The prevalence of hypertension in children increases rapidly. This paper is to investigate the association of vitamin A and serum 25(OH)D level with hypertension and to explore the risk factors of hypertension in children. 164 children  were included in this case-control study. The serum vitamin A and serum 25(OH)D level, the transcription level of RARs and RXRs, 25(OH)D receptor, and the retinol acyltransferase (LRAT), an indicator of vitamin A storage function, were measured. P=0.02). The transcription levels of RARα, RARβ, and RARγ were not significantly different between the two groups; but the LRAT was lower in the hypertensive group than that in the control (P<0.001). Compared with control group, the level of 25(OH)D receptor was lower in hypertension children (P=0.003). Logistic regression model showed that LRAT, HDL, and breastfed duration were negatively associated with blood pressure, and waist circumference was positively associated with blood pressure. The serum vitamin A level in hypertensive subjects was not significantly different compared to control, but the serum 25(OH)D level was significantly lower in hypertensive subjects compared to control D, and 25(OH)D receptor were significantly associated with blood pressure level, and both breastfed and HDL-C were independent protective factors of blood pressure level in children. Hypertension is a major risk factor for cardiovascular disease and stroke. It is one of the leading causes of death and disability worldwide. The prevalence of hypertension in children ranges from 3%-12.6% [In this study, we aim to explore the risk factors of hypertension in children. All-transretinoic acid (atRA), a biologically active metabolite of vitamin A (VA), has been shown to regulate the gene expression of components of rennin angiotensin system, including renin, angiotensin-converting enzyme, angiotensin II, and its type 1 receptor in animal studies . On the β) of 0.8 under the probability of type I error (α) of 0.05, with the parameter of VA mean 0.95 umol/L in case group and 1.05 umol/L in control group, standard deviation of 0.22, and using the formula n = (σ((zα/21− + zβ1−)/(μA − μB)))2, at least 76 samples were needed for case group and control group, respectively. A total of 164 gender and age (9.81±1.62 years) matched subjects were selected from an established cohort of 6102 children aged 6-12 years in 2013 in Chongqing from 6 elementary schools. Inclusion criteria for the hypertensive group were children aged 6 to 12 years diagnosed with hypertension [To achieve the power  was represented by father's occupation and father's education level, and the household income and family disease history of hypertension were also investigated.A semi-quantitative food frequency questionnaire was used to collect the dietary survey. Food was divided into 15 categories, including grains, vegetables, fruits, meat, poultry, fish and shellfish, eggs, milk and dairy products, beans and bean products, nuts, algae, cooking oil, pickles, nutritional supplements, and beverages. Cooking oil consumption was measured in a family unit, through collecting the frequency of eating at home for the family member and the total cooking oil consumption during a period, and then the average intake of cooking oil per day was estimated. The amount of food was investigated by interviewing the parents about the intake amount and the frequency during an interval, and then the total amount of food was averaged to the daily intake. The standardized food containing utensils  were used to display the weight of food to ensure the validity of survey.2), as a measure of general adiposity, and the Z-score of BMI was calculated using the LMS parameters and formula from CDC [Anthropometric measurements and other physical examinations were conduct by well-trained nurses. Waist circumference was measured twice at the center of the umbilicus over one T-shirt and the values were averaged. Height and weight were also measured by using mobile medical ultrasonic machine (the model is WS-H300D), and body mass index (BMI) was calculated as weight divided by squared height  and heart rate (HR) were measured on three separate occasions with participant in the sit-down position by the OMRON arm type electronic sphygmomanometer (HEM7051) using an appropriately sized BP cuff placed on the right arm. BP measurements were taken at 11, 13, and 15 minutes during a 15-minute relaxation period in one occasion . The aveThe venous blood (3ml) was drawn in the morning at least 12 hours after fasting and 24 hours after withholding from a high-fat diet and spicy diet for each subject. The serum was separated by 2500 rpm centrifugation at 4°C for 10 min. The automatic biochemical analyzer was used to measure the serum total cholesterol, high density lipoprotein cholesterol (HDL-C), triglyceride, low density lipoprotein cholesterol (LDL-C), and fasting blood glucose (FBG). The VA was measured by high performance liquid chromatography (HPLC) with dissolved mobile phase (which is made up of 97% methanol and 3% water). Anhydrous ethanol and n-hexane were used to extract retinol and dried by nitrogen. VD was also measured by HPLC, after extracting and filtering through acetonitrile and chromatographic column.α), retinoic acid receptor beta (RARβ), retinoic acid receptor γ(RARγ), LRAT, vitamin D receptor (VDR), and β-actin were provided in Supplementary β-actin using CFX Manager Software.The total RNA isolated from peripheral blood leukocyte was used for real-time polymerase chain reaction (PCR). A 500-ng sample of the total RNA was reverse-transcribed into cDNA using the PrimeScript® RT reagent kit  according to the protocol of manufacturer. Retinol acyltransferase (LRAT) was an indicator of vitamin A storage function. The primer sequences for human retinoic acid receptor alpha , and the Wilcoxon rank sum test was used for comparison between the two groups. The categorical variables were reported as numbers (n) and percentages of the total (%), and χ2 test was used to test the difference between two groups. Covariance analysis was used to adjust covariables, when comparing the concentration of serum retinol, 25(OH)D, and VDR between the two groups. Moreover, the correlation coefficients of blood pressure with LRAT, 25(OH)D, and VDR were analyzed by correlation analysis. Multivariate logistic regression model was used to identify the associations of hypertension and risk factors of VA and VD. Multivariate logistic regression model was used to identify the associations of hypertension and risk factors of VA and VD.The continuous variables were reported as means and standard deviations (SD) if the variables meet normal distribution, and t-test was used to test the significance of difference between the two groups. Continuous variables that do not satisfied the normal distribution were expressed as Xα level of 0.05.The data analysis for this study was generated using SAS 9.4 software . The t test and correlation analysis of VA, VD, and PCR in two groups were performed by Graph Pad Prism5 statistical software. Significant difference was determined at the  P<0.05)  . P<0.01)  were significantly higher in children with hypertension, but HDL-C was significantly lower in children with hypertension  . The tot P<0.01) .In Supplementary α, RARβ, and RARγ between the two groups  D was significantly correlated with DBP  . Howevero groups . The expo groups . The reso groups , but notwith DBP . Both thThe association of LRAT and VDR with BP was analyzed in multivariable logistic regression model in This study demonstrated that serum LRAT strongly correlated with blood pressure in children, and the serum 25(OH)D and its receptor VDR in children with hypertension were lower than those in the control group. The results showed that longer breastfed duration and higher HDL-C were the protective factors of hypertension, and abdominal obesity was associated with increased risk of hypertension in multivariable logistic regression model.α, β, and γ) in the peripheral blood have no significant difference between the two groups, which may be related to the delayed response of RARs, as retinoic acid receptor showed over expression when serum retinol was deficiency in the tissue. Whether there is VA deficiency in tissue in hypertensive children has not been reported yet, but study has shown that obesity, an important risk factor for hypertension, leads to functional VA deficiency in many organs with decreased expression of stellate cells markers  [LRAT level was negatively associated with blood pressure in this study. LRAT was a key enzyme in the transformation of retinol and retinyl esters and storage of serum retinol in the tissues . LRAT wa kidney) .The results also showed that the serum 25(OH)D and its receptor VDR had negative relationship with blood pressure. Serum 25(OH)D and VDR in children with hypertension were lower than those in the control group in univariate and multivariate regression analyses. Moreover, 25(OH)D deficiency was inversely associated with hypertension level, indicating that vitamin D depletion exacerbates hypertension by influencing VDR , 24. ThiLRAT expression level increased accompanying with the increase of VDR expression level in children with hypertension, suggesting VA associated with 25(OH)D in the blood pressure regulation process which need further research in future. Besides, HDL-C was negatively associated with blood pressure, consistent with other studies that show that higher HDL-C was likely to induce lower blood pressure level , and HDLIt is the first time that the negative relationship of LRAT and VDR with childhood hypertension was found, suggesting that supplement of VA and VD in children with hypertension may play important roles in cardiovascular protection. However, this study also has some limits. Because we did not conduct a prospective cohort study to explore the damage extent of VA and VD deficiency to the target organ of hypertension, it could not verify etiological hypothesis of VA and VD on children hypertension.Among children aged 6-12 years, serum LRAT, serum 25(OH)D, and VDR level were negatively associated with blood pressure level. These results suggest that improvement of VA and VD nutrition supply may be a potential usefulness intervention as hypotheses for further study. In addition, we found that longer breastfed duration was associated with decrease blood pressure level, suggesting that advocate breastfed was a potential method to control blood pressure level even in childhood. Besides, higher WC were related to deteriorated blood pressure level in children, suggesting through increasing exercise and healthy dietary to control obesity were valid methods to control blood pressure from childhood.


Patients with autosomal dominant polycystic kidney disease (ADPKD) have an increased risk of cardiovascular morbidity and mortality. Impaired left ventricular (LV) global longitudinal strain (GLS) can be a sign of subclinical cardiac dysfunction even in patients with otherwise preserved ejection fraction (EF). Transmitral early filling velocity to early diastolic strain rate (E/SRe) is a novel measure of LV filling pressure, which is often affected early in cardiac disease.A total of 110 ADPKD patients not on dialysis were included in this prospective study. All patients underwent an extensive echocardiographic examination including two-dimensional speckle tracking. GLS and strain rates were measured. The distribution of GLS and E/SRe was determined and patient characteristics were compared by median levels of GLS (− 17.8%) and E/SRe (91.4 cm). Twenty healthy participants were included as control group.p < 0.001. The same was true for E/SRe (mean: 10.0 ± 0.3 cm) compared to the control group (mean: 6.5 ± 0.3 cm), p < 0.001. In simple logistic regression, male gender , fasting glucose (odds ratio (OR) 1.05 [1.01–1.10], p = 0.024), htTKV , HDL cholesterol , triglycerides , hemoglobin , and β-blocker use  were all associated with higher GLS. After multivariate logistic regression with backward model selection, only male gender  and β-blocker use  remained significant. In simple logistic regression models, BMI , systolic blood pressure  and β-blocker use  were associated with higher E/SRe - a novel measure of left ventricular filling pressure. After backward elimination, only β-blocker use  remained significant.There was a significantly worse GLS in the ADPKD patients (mean: − 17.8 ± 2.5%) compared to the healthy controls (mean: − 21.9 ± 1.9%), Higher GLS and E/SRe are common in ADPKD patients, even in patients with preserved eGFR and normal left ventricular EF. GLS and E/SRe may aid in cardiovascular risk stratification in patients with ADPKD as they represent early markers of cardiac dysfunction.The online version of this article (10.1186/s12882-019-1500-1) contains supplementary material, which is available to authorized users. Individuals with autosomal dominant polycystic kidney disease (ADPKD) have a high prevalence of cardiovascular (CV) disease associated with significant morbidity and mortality . Death dLeft ventricular hypertrophy is a strong independent risk factor for CV morbidity and mortality and is highly prevalent in ADPKD patients, even in the absence of hypertension , 3. AlthPrevious understanding of CV risk in ADPKD has been achieved primarily through measurements of echocardiograms and cardiac magnetic resonance imaging , 4. The In a population of asymptomatic dialysis patients, two-dimensional speckle-tracking showed significantly higher (less negative) values of left ventricular peak longitudinal strain and early diastolic strain when compared to healthy individuals . SpeckleTwo-dimensional speckle-tracking has not previously been used to assess cardiac function in individuals with ADPKD. The aim of our study was 1) to investigate the distribution of GLS as assessed by two-dimensional speckle-tracking in asymptomatic patients with ADPKD and 2) to identify clinical variables associated with higher (less negative) strain measurements in these patients.2 were eligible to participate in a prospective observational cohort study at the Baltimore PKD Center at the University of Maryland School of Medicine. Patients with prior kidney transplant, pregnancy, uncontrolled diabetes (defined as a glycated hemoglobin > 7% or use of more than one anti-diabetic medication), current participation in an interventional pharmaceutical clinical trial, any systemic disease  likely to lead to kidney disease, or suspected kidney disease other than ADPKD were excluded. Participants were enrolled from 2013 through 2017. Family and personal medical history including absence of cardiac disease was obtained by nephrologist investigators through patient interview and review of medical records. Serum glucose, lipids and creatinine (using an IDMS-traceable assay) were measured after an overnight fast, and GFR was estimated using the creatinine-based CKD-Epi estimating equation ) compared to the healthy controls ]) , htTKV , fasting glucose , HDL , hemoglobin , triglycerides , and β-blocker use  were all associated with higher GLS (Table p = 0.014). According to the results of multiple logistic regression with backward elimination, male gender  and β-blocker use  were found to be strongly associated with higher GLS.In simple logistic regression, male gender , systolic blood pressure  and β-blocker use  were all independently associated with an increased E/SRe (> 91.4 cm). Based on the results of multiple variables logistic regression with stepwise backward elimination, only one variable remained significant: β-blocker use . The values found in our control group were similar to normative values in a large meta-analysis in healthy individuals (mean: − 19.7% +/− 0.4%) [In this prospective cohort study of adult ADPKD patients with no history of cardiac disease, we described the distribution of GLS relative to established clinical predictors of disease severity in ADPKD. Given that GLS has been demonstrated as an early and sensitive predictor of cardiovascular morbidity and mortality in other patient populations –23, it i/− 0.4%) . As bothLongitudinal strain is known to be influenced by several clinical factors such as diabetes , obesityAs more cysts develop, the renin-angiotensin-aldosterone system (RAAS) is activated leading to high blood pressure very early in the pathogenesis . TherefoDiastolic dysfunction assessed according to current recommendations  was presWe also found that more men had higher GLS than women. This is consistent with reports that CV disease in men with ADPKD is more severe  and it iOur study had some limitations. This was a single-center study. Participants had relatively preserved renal function, and the majority were Caucasian. Although none of these patients had diabetes requiring insulin, we do not have data on measures of insulin sensitivity. Furthermore, we did not have information regarding treatment with erythropoietin stimulating agents (ESA). Nevertheless, this is the first study to our knowledge to apply speckle echo images in adults with ADPKD. Although speckle echo represents a novel technology not generally available in general clinical practice, strain measurements can be applied to standard echo images, making this approach potentially easier and more cost effective for clinical risk stratification than cardiac MRI . FinallyHigher (worse) GLS and elevated LV filling pressure assessed by E/SRe are common in patients suffering from autosomal dominant polycystic kidney disease, even those with preserved eGFR and LVEF. These measures may represent early markers of cardiac dysfunction that may be used for cardiovascular risk stratification in autosomal dominant polycystic kidney disease. Use of sensitive measurements from speckle echo may be of benefit in elucidating mechanisms of early cardiovascular disease onset in early stage ADPKD.Additional file 1:Table S1A. Associations with GLS, Linear Regression . Table S1B. Associations with E/SRe, Linear Regression . Table S2A. Associations with GLS: Logistic regression . Table S2B. Associations with E/SRe: Logistic regression . (DOCX 18 kb)


Hypertension is known as the major risk factor for cardiovascular mortality and morbidity. Antihypertensive agents are directed to prevent many of the harmful effects of elevated blood pressure, yet medication nonadherence hinders the effectiveness of these therapies. Nowadays the use of mobile phone has vastly spread among communities. The rapid adoption of smartphone technology creates a promising and interesting platform to overcome medication nonadherence. This review aimed to critically appraise whether mobile phone-based interventions are effective in increasing adherence in hypertensive patients. Literature searching was done in 3 databases: PubMed, Cochrane, and ProQuest. Findings were narrowed down using selection criteria. Relevant studies were to be critically appraised based on the guideline from Centre for Evidence-Based Medicine, Oxford University. We found that the reduction of blood pressure in participants who were given reminder through mobile phones was greater in comparison to control: systolic , diastolic . Patients who were nonadherent at baseline benefit more from mobile phone-based intervention in comparison to adherent patients at baseline: RR 2.3  vs RR 1.3 . In conclusion, mobile phone-based interventions were effective in increasing medication adherence in hypertensive patients. Clinical practice guidelines should consider this nonpharmacological method for a better blood pressure regulation. Hypertension is defined as a systolic blood pressure greater than 140 mmHg and a diastolic blood pressure greater than 90 mmHg from an average of at least 2 measurements . HyperteA 62-year-old woman came to a clinic with a worsening headache for the past 3 days. The pain was felt continuously, such as being pressed on the back of the head, was not pulsatile, and was of moderate intensity. Complaints of nausea, vomiting, decreased consciousness, visual disturbances, slurred speech, or body weaknesses were denied. A history of head trauma was also denied. The patient said that such complaint was often experienced during high blood pressure. The patient was diagnosed with hypertension 10 years ago. She had been given antihypertensive drugs but did not consume them routinely. Her highest blood pressure was 180 mmHg with an average of 150–160 mmHg. She usually visits the clinic and takes her medication only when complaints are present. She does not regularly take her medication because she often forgets and feels no symptoms. In physical examination, her blood pressure was 150/100 mmHg; other vital signs were within normal limits. Visual Analogue Scale (VAS) was 6–7 at the occiput region, with no tenderness nor inflammation. Other physical examinations were within normal limits.Based on the presented case illustration above, we formulate a clinical question, “How does mobile phone-based intervention affect the medication adherence of hypertensive patients?”Patient(P): hypertensive patientIntervention (I): mobile phone-based interventionComparison (C): standard careOutcome (O): adherenceHence, the PICO framework derived from the question above is as follows:Data for this review were identified through searches. Literature searching was performed in 3 databases: PubMed, Cochrane, and ProQuest on December 15th 2018. Only articles published in the last 5 years were included. The terms found in PICO were formulated using Boolean technique to be used as keywords in each database . SubsequIn this review, we examined the efficacy of mobile phone-based intervention in increasing medication adherence in hypertensive patients. We found 158 records using the search strategy noted in In terms of validity, the study by Kim et al. had a low validity value due to the absence of blinding technique; hence treatment allocation was disclosed although participants had already been randomized. In addition, out of 160 participants who were randomized, only 95 participants left at the end of trial (loss to follow-up >20%). Therefore, this is not in accordance with the intention-to-treat principle. The remaining 4 clinical trials were considered valid . Two systematic reviews were also considered valid.In terms of importance, 3 studies had low scores. Those include studies by Davidson et al., Kim et al., and Bobrow et al. In the study by Davidson et al., the data of control group was less presented than the intervention group. Consequently, its clinical importance and the statistical significance were not clear. In the study by Kim and colleagues, the intervention did not bring about a large nor significant effect in treatment group when compared to the control group. However, note that their study participants were taken from hospital employees and their relatives who had better health knowledge and considerably adherent background. Thus, the study results may not reflect that of general population and its clinical importance remains uncertain. The results of the study from Bobrow et al. did not display a robust enough evidence due to the wide data distribution (poor precision) so that poor adherence was also found in the intervention group. In other words, their intervention did not succesfully increase patients' adherence. The remaining 2 studies had clinically important results.In terms of applicability, the most practical study—relating to the case illustration—would be the study by Varletta et al. on the basis of the similarity of basic characteristics of the study population  and the type of intervention that was in the form of text messages (simple). In contrast, the studies most difficult to apply to our patient would be those of Davidson and Kim due to the fact that their intervention involved monitor devices connected to mobile phones  and the high educational background of their participants.There were various forms of interventions: from the conventional text messages (SMS) to smartphone applications, and a more sophisticated method that involved an external monitoring device. Bobrow et al. utilized text messages to provide medication motivations along with education about hypertension and its treatment . VarlettThe primary endpoint is medication adherence after mobile phone-based intervention. Another outcome of interest is blood pressure changes as a result of medication adherence. Based on literature, medication adherence is defined as the degree to which a patient follows the prescribed dosage, frequency, and timing of drug intake . To measPoor blood pressure control has a negative impact on the course of hypertension by causing various complications. Antihypertensive agents are directed to prevent many of the harmful effects of elevated blood pressure, yet medication nonadherence hinders the effectiveness of these therapies . This reOverall, studies found a tendency of increased medication adherence levels in hypertensive patients as a result of mobile phone-based interventions. Although the types of interventions and adherence parameters vary across studies, the results are in line with one another. This enhances the value of an intervention because the results are consistent when measured using various criteria.Mobile phone-based intervention can be divided grossly into 2 types: text messages and smartphone applications. Both have the role of providing a drug intake reminder, an independent blood pressure monitoring reminder, or a routine clinic visit reminder. This is crucial given that it is not uncommon to encounter hypertensive patients who take their drugs and pay a clinic visit only when complaints are present, making preventive roles of antihypertensives inefficient. After studies are conducted, it was found that patients who were given reminders had better blood pressure control , 10.There are differences in the frequency of sending drug reminders between studies: at every dosing time , every dAside from medication adherence, blood pressure control is also influenced by other factors including drug dose, antihypertensives agent, and lifestyle. Therefore, in addition to a reminder feature, mobile phone-based intervention can also be complemented by other features such as motivational messages, educational information regarding healthy lifestyle for hypertensive patients, the importance of consuming drugs regularly, or educational information regarding hypertension in general , 8, 9. TIn the form of an application, several additional features—like keeping a record of blood pressure measurements, displaying a tailored blood pressure target, and physician's note on the patient's antihypertensive —can be aTranslating this review into clinical practice, we recommend a study to be conducted on the subject of mobile phone-based intervention efficacy in hypertensive patients in Indonesia prior to applying such therapy to patients given the absence of similar intervention technique in Indonesia. Furthermore, future research should also focus on evaluating the appropriate reminder frequency and the type of intervention that is best applied. It is worth noting that the studies by Davidson et al.  and Kim Mobile phone-based interventions were effective in increasing medication and blood pressure monitoring adherence in hypertensive patients. Given the high burden of uncontrolled hypertension worldwide, this nonpharmacological strategy could be considered as an adjunct to antihypertensive medication. Nonetheless, such intervention should be developed further before being applied in daily practice.


Intra-abdominal pressure (IAP) is a physiological parameter that has gained considerable attention during the last few decades. The incidence of complications arising from increased IAP, known as intra-abdominal hypertension (IAH) or abdominal compartment syndrome in critically ill patients, is high and its impact is significant. The effects of IAP in neurological conditions and during surgical procedures are largely unexplored. IAP also appears to be relevant during neurosurgical procedures (spine and brain) in the prone position, and in selected cases, IAH may affect cerebrospinal fluid drainage after a ventriculoperitoneal shunt operation. Furthermore, raised IAP is one of the contributors to intracranial hypertension in patients with morbid obesity. In traumatic brain injury, case reports described how abdominal decompression lowers intracerebral pressure. The anatomical substrate for transmission of the IAP to the brain and venous system of the spine is the extradural neural axis compartment; the first reports of this phenomenon can be found in anatomical studies of the sixteenth century. In this review, we summarize the available knowledge on how IAP impacts the cerebrospinal venous system and the jugular venous system via two pathways, and we discuss the implications for neurosurgical procedures as well as the relevance of IAH in neurological disorders. Increased intra-abdominal pressure (IAP) is recognized as a significant contributor to organ dysfunction in many critically ill patients. Although it primarily has been studied in surgical ICU patients suffering from abdominal catastrophes such as abdominal trauma, peritonitis, and pancreatitis, it has also been associated with massive fluid resuscitation.IAP is defined as the steady-state pressure within the abdominal cavity. Under physiological conditions, values of up to 5 mmHg are considered normal in adults . IAP varIntra-abdominal hypertension (IAH) is defined as a sustained IAP elevation equal to or above 12 mmHg, usually documented in three consecutive measurements taken at 4- to 6-h intervals. Since 2004, the World Society of the Abdominal Compartment Syndrome  has developed a cohesive approach to the management of IAH and ACS, fostered education and research, and developed consensus statements and definitions . RecentlWhile the impact of elevated IAP has been described anecdotally in neurological conditions, the anatomy and pathophysiology of the related vascular structures have not yet been described in detail. In this manuscript, we will focus on both issues and review the literature on the relevance and impact of elevated IAP in neurological and neurosurgical practice.Relevant articles were identified by searching PubMed from 1918 to 2018 and also by screening the references of the identified articles.The following search items were used: “Intra-abdominal pressure AND neurosurgery,” “intra-abdominal pressure AND spine surgery,” “intra-abdominal pressure AND TBI,” “intra-abdominal pressure AND hydrocephalus,” “intra-abdominal pressure AND IIH”.After the search by the first author, all literature was reviewed by the coauthors and supplemented with relevant articles. The coauthors are experts in various areas related to IAP: history, neuroanatomy, intensive care medicine, and neurosurgery.The relationship between the IAP and the intracranial pressure (ICP) has been suspected for more than 100 years.The existence of both the cranial venous system and the vertebral venous system (VVS) was already known in the sixteenth century, but it was Breschet in 1828–1832 who published the first detailed drawings, accurately visualizing the multiple anastomoses c.q. the anatomical connections between the intracranial venous system and the VVS.In 1940, the first of Batson’s two landmark articles appeared, dealing with properties of the spinal veins. His radiological study provided an explanation for the spread of metastasis and infections through these vertebral veins, into the spine and the central nervous system . Batson’Multiple anatomical studies over the past century have shown that the cranial and vertebral venous system has connections to both the deep systemic, valved venous system, including the inferior and superior vena cava, to the valveless superficial veins in the face, head, and back and to the thoracoabdominal wall , 26, 30 In 2000, Dwight Parkinson described the extradural neural axis compartment (EDNAC), which is characterized by valveless veins that allow blood to run freely in either direction between the orbit and the os coccygis . Later, The pivotal system responsible for the regulation of pressure within the spinal canal and partially within the intradural compartment seems to be the venous structures belonging to the extradural neural axis compartment. The vertebral venous system is a part of that structure and parallels, joins, and at the same time bypasses the longitudinal veins of the thoracoabdominal cavity. The VVS is connected with both the superior and the inferior vena cava by means of numerous connections with the intrathoracic (hemi)azygos venous system and the intra-abdominal lumbar veins. Also, numerous connections exist with the subcutaneous veins of the chest and the abdomen, the vertebral veins of the neck, and the sacral venous plexus.Since the VVS is valveless, flow and the direction of flow depend (1) on pressure gradients between the IAP, the intrathoracic pressure (ITP) and the pressure in the spinal canal which is largely determined by the ICP; and (2) on hydrostatic factors and gravitation forces that may occur with changing of posture or position .Morphological features that seem of the utmost importance are the fact (1) that the VVS has a large volume (probably 20 times larger than that of the contributing arteries ); (2) thTwo important mechanisms are involved in the interaction between the abdominal compartment and the central nervous system. In the first mechanism, the VVS is the anatomical substrate for transmission of the IAP to the spinal canal and the cranium.This valveless VVS, which allows bidirectional flow, is a huge reservoir for blood. Pressure change in one compartment of the human body and can thus shift venous blood to the other compartment. Epstein and colleagues described this as a large-capacity “venous lake,” out of which blood may flow into the brain and spinal canal and into which blood may flow from the brain, depending on variations in posture and thoracic pressure or IAP .Secondly, an increased IAP has an influence on the intrathoracic pressure (ITP). Cerebrospinal fluid (CSF) and the brain’s venous drainage both leave the brain via the jugular veins and the VVS. Elevations in the IAP are transferred into the thoracic compartment, which in turn results in a back pressure on the jugular veins and decreases the drainage of the CSF and blood, leading to an increased ICP , 43  is part of the dura mater and the optic nerve is surrounded by CSF, a change in pressure within the subarachnoid space is detected by ultrasonography. An analysis of prospectively collected data of patients who underwent laparoscopic procedures showed that an acute elevation in IAP significantly increased the optic nerve sheath diameter (ONSD). The changes in the ONSD reflect a temporary and reversible increase in ICP . Recent The intravesicular IAP measurement is convenient and is considered the gold standard , 58. IAP2O). In a prospective comparative study, Al-Abassi et al. showed that intra-bladder pressure measurement is a simple, minimally invasive method that may reliably estimate the IAP in patients placed in supine position [Conditions for a reproducible intravesicular IAP measurement are measured at end-expiration; performed in the supine position; zeroed at the iliac crest in the mid-axillary line, using a priming volume in the bladder of < 25 mL of saline; measured 30–60 s after instillation to allow for bladder detrusor muscle; and measured in the absence of active abdominal muscle contractions. Values need to be expressed in millimeters of mercury , a free-hanging abdomen is mandatory to prevent venous congestion of the operative field , 8. PrioOne of the implications of inadequate positioning during spine surgery in the prone position is the increased blood loss associated with the higher IAP values that were described in some studies. A rise in IAP can cause venous congestion in the pelvis and abdomen. This may lead to backflow of venous blood into large valveless VVS, which can result in venous congestion in the rigid spinal canal, which makes spinal surgery complicated , 51 Fig.The study by Han et al. was the first prospective study to show the effect of BMI on IAP and intra-operative blood loss during spinal surgery. Besides this cumbersome blood loss, the visual operating field is obscured, making microsurgery a more difficult and frequently a higher complexity procedure because of the risk of damaging neurological structures and creating temporary or permanent postoperative loss of function.Another consequence of inadequate positioning can be brain swelling during posterior fossa surgery or supratentorial craniotomy in the prone position. As mentioned earlier, raised IAP causes a rise of the intrathoracic pressure. This causes an increase in back pressure in the jugular veins and decreased drainage of venous blood and CSF Fig. .Fig. 5ScHowever, it is clearly not yet common knowledge that venous congestion in the spinal canal is a problem in surgery in prone position and that this problem involves the IAP. In a review by Chui et al. about the prevention of complications related to prone positioning during spinal surgery, the reviewers did not consider the importance of a free abdomen to reduce the incidence of postoperative visual loss was not considered , 22.In the neurosurgical community, IAP is regarded as a negligible variable when considering the use of a ventriculoperitoneal shunt for treating hydrocephalus. It is a general misconception in the neurosurgical community that IAP is around 0 mmHg and therefore does not interfere with CSF drainage into the peritoneal cavity.A study performed by Sahuquillo et al. on 60 patients requiring a ventriculoperitoneal shunt evaluated the relationship between body mass index (BMI) and IAP and provided data to estimate IAP in order to help neurosurgeons with the selection of the appropriate shunt. IAP was measured through an intraperitoneal catheter during shunt surgery. The authors concluded that in obese and overweight patients, neurosurgeons should take IAP into account when selecting both the most adequate differential pressure valve and the distal cavity to place the distal catheter. IAH could be a reason to choose another distal cavity, for example the pleural cavity , 55.Therefore, in the event of neurologic deterioration in patients with a pre-existing ventriculoperitoneal shunt during critical illness, IAP should be monitored and IAH should be treated promptly. IAP should also be monitored in critically ill, sedated, and mechanically ventilated patients with a ventriculoperitoneal shunt, since neurologic examination is unreliable in these circumstances.Raised IAP due to constipation, ileus, or small-bowel obstruction has also been reported to play a role in malfunctioning ventriculoperitoneal shunts in patients with hydrocephalus .Various case reports have described raised ICP following abdominal closure after laparotomy in polytrauma patient. A patient whose acute subdural hematoma was removed in combination with a splenectomy for trauma-developed acute bleeding from his right transverse sinus and brain herniation as the abdomen was closed, indicating a rise in venous pressure .The first well-conducted clinical study evaluating the relationship between IAP and ICP in 15 patients with traumatic brain injury was published by Citerio et al. in 2001 . They coA number of publications reported decompressive laparotomy (DL) as a last resort to decrease otherwise untreatable intracranial hypertension after TBI. In one series, abdominal fascia release resulted in the decrease of ICP in 11 out of 17 patients. All 11 patients survived .2O, and one patient even achieved a value of 47 cmH2O. The authors were prompted to perform this study after the observation that patients were referred for fundoscopy due to increased CSF pressure while they had no symptoms of intracranial hypertension.In a study by Neville et al., 15 patients with normal opening pressures on lumbar puncture and referred for CSF analysis were asked to artificially increase their IAP through a Valsalva maneuver . All werp < 0.05) [In a series of 102 patients who sustained blunt brain injury, Scalea et al. evaluated the serial application of decompressive craniectomy (DC) and decompressive laparotomy (DL) to treat multicompartment syndrome (MCS) and to lower ICP; 24% of the patients required both interventions. Fifteen patients had DC before DL and nine had DL before DC. The mean time between DC and DL was 3.4 ± 6 days. Mean ICP decreased significantly after both DC and DL ( < 0.05) .In a recent review, Lauerman et al. described the pathophysiology of a multicompartment syndrome (MCS) and current treatment considerations for patients with TBI given the effect of MCS. In MCS, intracranial, intrathoracic, and intra-abdominal compartment pressures are interrelated. The authors concluded that TBI care should include ICP control as well as minimization of intrathoracic and intra-abdominal pressure as far as clinically possible .Another indication of the link between cerebral venous outflow and ICP is the beneficial effect on a raised ICP in TBI that is achieved by elevating the head of the bed . AnotherIdiopathic intracranial hypertension (IIH) is characterized by an elevation of intracranial pressure (ICP). In the primary form, there is no identifiable cause. IIH is a disorder that mainly affects obese women of childbearing age. Its prevalence has been estimated to lie between 0.5 and 2 per 100,000 of the general population. Clinical symptoms include headache; visual disturbances due to papilloedema and, less frequently, olfactory dysfunction; uni- or bilateral pulsatile tinnitus; diplopia due to sixth nerve palsy; and cognitive dysfunction . ObesityThe jugular venous system is commonly recognized as the main route of venous efflux from the brain. However, the jugular venous system has important flow limitations with changes in posture as described earlier in the pathophysiology . A volumOther studies confirmed that the anastomoses between the cranial and vertebral portions of the CSVS appear to serve an important function in providing pressure homeostasis to the intracranial venous system with changes in posture , 28, 60.Besides the anatomical variations of cerebral venous drainage, there is also a variation in abdominal compliance . AbdominThe balance between cerebral blood inflow and outflow is vital in maintaining normal ICP. Restrictions in venous outflow, for example due to a raised IAP, can be as important as mass accumulation within the cranium, if not more so  Fig. 5)5).The increased IAP in obese patients can thus influence ICP via the two pathways described in this literature review. The relationship between obesity and the onset of IIH is unclear for many reasons: first, there are many anatomical variants of venous drainage; second, there are differences in abdominal compliance between patients; and last, it is unclear by which pathway IAP has the most influence on ICP .The IAP is an important physiological parameter in neurosurgery and neurology. It has a close relationship with the ICP, and current evidence supports the concept that there are two pathways by which the IAP can be transmitted to the central nervous system. One pathway is by backflow through the venous plexus of the spinal canal and the intracranial veins. This valveless venous plexus provides a direct anatomic route from the pelvis to the eyes and the brain, and vice versa. This is a route with numerous anastomoses to the systemic venous circulation, including the venous circulation of the lungs, the renal veins, and the veins of the breasts. The second pathway is a direct effect via an increase in IAP, which causes a cranial excursion of the diaphragm. The elevated intrathoracic pressure and augmented central venous pressure causes a decrease in venous drainage from the central nervous system via the jugular system.Current evidence suggests that increased IAP may play an important role during neurosurgical procedures in patients suffering from IIH or TBI and during hydrocephalus therapy. IAP measurement could provide relevant information to improve the safety of surgical procedures in spine surgery and posterior fossa surgery. Furthermore, it could optimize the treatment for IIH, TBI, and hydrocephalus. However, more prospective research in this field is needed.


Mortal Kombat) or a puzzle game (Tetris). Study outcomes were heart rate variability, systolic and diastolic blood pressure, and positive and negative emotion ratings measured before, during and after gameplay. Results indicated that threat appraisal instructions increased negative emotion ratings and decreased heart rate variability, but not blood pressure, which is an essential marker for cardiovascular stress responses. Increased blood pressure and decreased heart rate variability was associated with fighting game players when compared with the puzzle game players, indicating a cardiovascular stress response; however, fighting game players also reported higher positive emotion ratings. Based on the study findings, video games do not induce stress responses like mental stressors used in previous research, demonstrating that the interactive player experience in video gaming may have more complex effects on stress outcomes. Future research should comprehensively measure biopsychosocial stress indicators and multiple emotional states over time to fully examine the relationship between video games and stress.Although previous studies have found that video games induce stress, studies have not typically measured all salient indicators of stress responses including stress appraisals, cardiovascular indicators, and emotion outcomes. The current study used the Biopsychosocial Model of Challenge and Threat  to deter In recent years, research has demonstrated an interest in the effects of video games on stress. Some research studies have found that video games induce stress , while oStress is an important predictor of long term health. Chronic stress over time influences cardiovascular, metabolic, and immunological dysfunction, and contributes to the progression and exacerbation of multiple health problems including coronary heart disease, autoimmune disease, and diabetes . ChronicWhen encountering a stressor in the environment, the body activates a physiological stress response. During a stress response, the central, autonomic, endocrine, and immune regulatory systems interact to adapt to stressor demands and achieve physiological stability . As descHowever, newer stress theories state that encountering a stressor does not always activate a physiological stress response, and the activation of a stress response is dependent on a cognitive process known as stress appraisal . During The Biopsychosocial Model of Challenge and Threat  added toThe Biopsychosocial Model of Challenge and Threat  also desBased on study findings with the Biopsychosocial Model of Challenge and Threat , threat In addition, previous video game studies have a limited focus on emotion. Studies with stress outcomes and violent video games have measured negative emotions such as anger, hostility, fear, and anxiety , withoutThe stress appraisal literature supports this need to measure a wider range of emotional states over time. According to To add to the current literature, the current study manipulated stress appraisals before video gameplay and examined if cardiovascular and emotional outcomes as described in the Biopsychosocial Model of Challenge and Threat  can be rWe expect that threat and challenge instructions will result in decreased heart rate variability during and post-gameplay when compared to baseline, but the groups will differ in blood pressure changes. Participants who play under threat instructions are expected to show increased blood pressure while challenge instructions are not predicted to have an impact on blood pressure. Instruction groups are also predicted to differ in their emotion ratings. In comparison to challenge instructions, threat instructions should be associated with higher negative emotion ratings and lower positive emotion ratings post-gameplay.Conflict Desert Storm) increased heart rate while a non-violent game (Hard Hitter Tennis) decreased heart rate during gameplay. Other studies have demonstrated similar findings, and after playing video games involving fighting or shooting other human avatars such as Mortal Kombat or Call of Duty, participants have shown increases in heart rate, blood pressure, respiration rate, and decreases in heart rate variability  that represent different kinds of game content to test whether they would influence outcome measures as suggested by past research or would interact with the threat and challenge appraisal instructions. In this way, we would be able to assess the degree to which the findings can be generalized across at least two kinds of video games or can be specialized within a specific kind of video game.Also of interest to the study is whether the emotional and cardiovascular changes associated with gameplay would be influenced by video game content. In a previous study, iability . Converson rates . BecauseM = 19.92, SD = 3.18), and were 60% male and 60% White. All participants reported playing video games at least once before . On average, participants played games at least once a week  for about 7 h a week . Participants perceived themselves as moderately skilled at playing video games . At baseline, participants showed normal levels of systolic blood pressure  and diastolic blood pressure . Only 2% of participants reported a previous diagnosis related to blood pressure outcomes including hypertension, diabetes, or renal disease. This study was carried out in accordance with the guidelines for human subjects in research and approved by The UNC Charlotte Institutional Review Board (IRB). All participants gave written informed consent in accordance with the Declaration of Helsinki, and received course credit for their participation.One hundred and forty-eight psychology students at The University of North Carolina at Charlotte participated in this study. Participant ages ranged from 18 to 38 , which is a recommended time domain measure for short-term heart rate variability estimates . Lower RPositive and negative emotion ratings were measured based on a previous study done by Previous video game experience was measured as a potential confound at baseline. Challenge and threat appraisals are influenced by perceived resources to cope with tasks demands, including previous experience or skills . For exaMortal Kombat players, experimenters recorded the number of matches won out of ten. For Tetris players, experimenters recorded the highest number of points won during the level. Game performance scores were used to compare performance for threat and challenge appraisal groups within each of the game content conditions. Due to the use of different scoring metrics, performance was not compared between the two games.Participant performance was assessed as a secondary measure of stress appraisal effects and was recorded during gameplay by the experimenter. For Mortal Kombat or Tetris, participants rated their game experience using an investigator developed, five-point Likert scale . Participants rated the game on each of the following characteristics: violent, boring, enjoyable, and difficult.After playing Several measures of physical health were collected at baseline to assess potential confounds for blood pressure outcomes. Body Mass Index was measured using a stadiometer and electronic scale, and participants were asked if they currently smoked, drank alcohol, and if they were previously diagnosed with hypertension, diabetes, or renal disease. Participants were also asked if they ingested caffeine within the last 4 h.Polar monitor. After sitting quietly for 5 min, three blood pressure readings were measured using an Omron cuff.The current study used a factorial design with two between subject variables  and repeated measures at three time points: baseline, pre-gameplay, and post-gameplay. Participants were run individually in 1 h sessions, and randomly assigned to one of four conditions based on appraisal instructions and video game content. There were 37 participants per group. The four conditions were: challenge-fighting, threat-fighting, challenge-puzzle, and threat-puzzle. All four conditions were balanced by gender. At baseline, background video game experience and health indicator questionnaires were given to participants, and emotion ratings scales, heart rate variability, and blood pressure were measured. To measure heart rate variability continuously, participants wore a chest strap and Mortal Kombat or get 50,000 points in Tetris Ultimate), and were told they “would be evaluated based on their game performance and the speed with which they play the game.” After instructions, participants completed pre-gameplay primary and secondary stress appraisal ratings, emotion ratings, and two blood pressure readings. Participants were not given time to practice the controls before playing the video game.Video game instructions differed based on condition assignment and were developed from previous appraisal research . ParticiMortal Kombat = number of matches won out of ten; Tetris Ultimate = highest number of points achieved within a single round). At 5 and 10 min of gameplay, the experimenter gave additional verbal prompts based on condition assignment. At 5 min, threat condition participants were told “You have 10 min remaining. You need to win matches/get points as fast as possible” and challenge condition participants were told “We want to see how you persist during a challenge, so don’t give up and win as many matches/get the highest score you can.” At 10 min, threat condition participants were told “You have 5 min remaining. You need to play faster and win more matches/get a higher score” and challenge condition participants were told “You’ll improve as you keep trying. Don’t give up.” Post-gameplay, participants completed stress appraisal ratings, emotion ratings, and game characteristic ratings , and three final blood pressure readings were collected.Participants played the video game for 15 min and the experimenter recorded game performance ((ANOVAs) to determine main and interaction effects of the two between-group variables: appraisal instructions , and video game content (fighting or puzzle) with time as the repeated measures variable. Blood pressure readings, heart rate variability readings, and emotion ratings were analyzed at baseline, pre-gameplay, and post-gameplay. Heart rate variability changes were also continuously measured while playing the game and continuous readings were averaged and analyzed across 5-min intervals: baseline, before gameplay, 0–5 min of gameplay, 5–10 min, 10–15 min, and after gameplay. Blood pressure scores were averaged across two or three readings within 1-min intervals. F-tests reported for all within-group effects include the Greenhouse–Geisser correction when necessary to protect against possible violation of the sphericity assumption. Post hoc Bonferroni were used to examine main effects and simple main effects were analyzed to follow-up significant interaction effects. A significance level of 0.05 was used for all statistical tests.Data were analyzed using SPSS version 23. Study outcomes were examined separately using mixed analysis of variances ANOVAs or Chi-Square tests. The data showing no significant differences among the groups are presented in 2  = 0.98, p = 0.32, or fighting game preference, χ2  = 2.08, p = 0.15. Bivariate correlations for pre-gameplay and post-gameplay dependent variables are shown in Group differences in background video game experience, health indicators, and baseline measures were examined with a series of one-way ANOVAs were used to examine demand appraisals and skill appraisals at pre and post-gameplay. We predicted that threat appraisal instructions would result in higher demand appraisal ratings and lower skill appraisal ratings compared to challenge appraisal instructions. There was a significant main effect of challenge and threat instructions on demand appraisal ratings, F = 12.35, p < 0.001, ηp2 = 0.08, and skill appraisal ratings, F = 17.56, p < 0.001, ηp2 = 0.11. There were also significant interaction effects of appraisal instructions on demand appraisal ratings from pre to post-gameplay, F = 3.88, p < 0.05, ηp2 = 0.03, and skill appraisal ratings, F = 17.56, p < 0.001, ηp2 = 0.11. An analysis of simple main effects showed that threat appraisal groups had significantly higher demand ratings than challenge groups pre-gameplay, F = 3.98, p < 0.05, and post-gameplay, F = 15.91, p < 0.001. In addition, threat appraisal groups had significantly lower skill ratings post-gameplay, F = 24.88, p < 0.001, but no significant differences pre-gameplay, F = 1.37, p = 0.24. Compared to the challenge instruction groups, participants who received threat instructions believed the game was more demanding before and after the game, and they believed they were less skilled after playing the game. This indicated that the threat instructions worked as expected.Mixed 2 × 2 F = 3.88, p = 0.18, or skill appraisal, F = 0.34, p = 0.34, but there was a significant interaction effect of game content over time for skill appraisal, F = 8.81, p < 0.01, ηp2 = 0.06. An analysis of simple main effects showed that Tetris players had significantly higher skill appraisal ratings pre-gameplay, F = 8.98, p < 0.01, indicating that they believed they would be more skilled at the game than Mortal Kombat players.We also examined how game content influenced demand appraisals and skill appraisals. There was not a main effect of game content on demand appraisal, ANOVAs. There was a significant difference across groups for game violence ratings, boredom ratings, enjoyment ratings, and difficulty ratings  = 7.46, p < 0.001, ηp2 = 0.05; but there was no significant main effect of appraisal instructions, F = 0.58, p = 0.45. An analysis of simple main effects showed that threat appraisal groups had significantly lower RMSSD than challenge groups during the first 5 min of gameplay, F = 3.88, p < 0.05; but there were no other significant simple effects at other time points: pre-gameplay, F < 1, between 5 and 10 min of gameplay, F = 1.40, p = 0.24, between 10 and 15 min of gameplay, F = 3.23 p = 0.07, or post-gameplay, F < 1. In conclusion, participants who received threat appraisal instructions had more sympathetic activity during the start of the game, and Changes in heart rate variability before, during and after game play were analyzed using a series of mixed sion see . As showF = 0.95, p = 0.33, but F = 4.15, p < 0.01, ηp2 = 0.03. An analysis of simple main effects showed that Mortal Kombat players had significantly lower RMSSD than Tetris players during the last 5 min of gameplay, F = 4.49, p < 0.05. There were no significant simple main effects at other time points pre-gameplay, F < 1, between 0 and 5 min of gameplay, F = 2.19, p = 0.14, between 5 and 10 min of gameplay, F = 2.20 p = 0.14, or post-gameplay, F < 1. In conclusion, Mortal Kombat players had lower RMSSD during the last few minutes of the game, and F = 2.22, p = 0.14, or significant appraisal × game content interaction over time, F < 1.There was not a significant main effect of game content on RMSSD, F = 0.07, p = 0.79, or diastolic blood pressure, F = 1.12, p = 0.29. There were also no interaction effects of instructions over time on systolic, F = 1.01, p = 0.36, or diastolic blood pressure, F = 0.83, p = 0.43. Thus, appraisal instructions had no effect on blood pressure.Systolic and diastolic blood pressure also varied significantly over time in the experimental session. F = 1.64, p = 0.20, or diastolic blood pressure, F = 0.78, p = 0.38, but there were interaction effects of game content over time on systolic, F = 13.64, p < 0.001, ηp2 = 0.09, and diastolic blood pressure, F = 5.54, p < 0.01, ηp2 = 0.04. An analysis of simple main effects showed that Mortal Kombat players had higher systolic blood pressure than Tetris players post-gameplay, F = 6.74, p < 0.01. There were no significant simple main effects at baseline, F < 1 or pre-gameplay, F < 1.There were no main effects of game content on systolic, F < 1, pre-gameplay, F < 1, or post-gameplay, F = 2.41, p = 0.12. To investigate further, we examined the simple main effects of time when holding game content as a constant, and we found significant effects for both Tetris, F = 7.25, p < 0.001, and Mortal Kombat, F = 18.71, p < 0.001. As shown in Tetris groups had a significant decrease in diastolic blood pressure after receiving instructions, and blood pressure significantly increased to baseline levels after the game. Both Mortal Kombat groups had a significant increase in blood pressure after the game. This indicates that Mortal Kombat players experienced a cardiovascular stress response while Tetris players did not.There were no significant simple main effects for diastolic blood pressure at baseline, F = 1.07, p = 0.30, or diastolic blood pressure, F < 1. There was also no appraisal × game content interaction over time for systolic, F < 1, or diastolic blood pressure, F < 1.There was no appraisal × game content interaction for systolic, F = 4.18, p < 0.05, ηp2 = 0.03, challenge emotions, F = 6.60, p < 0.01, ηp2 = 0.04, and benefit emotions, F = 5.43, p < 0.05, ηp2 = 0.04. There were also significant interaction effects of appraisal instructions over time for all emotion subscales including threat emotions, F = 3.24, p < 0.05, ηp2 = 0.02, challenge emotions, F = 6.44, p < 0.01, ηp2 = 0.04, harm emotions, F = 13.74, p < 0.001, ηp2 = 0.09, and benefit emotions, F = 10.39, p < 0.001, ηp2 = 0.07.As indicated by the data presented in F = 7.69, p < 0.01, but not post-gameplay, F = 3.04, p = 0.08. Post-gameplay, threat appraisal groups reported significantly lower challenge emotion ratings, F = 13.51, p < 0.001, higher harm emotion ratings post-gameplay, F = 11.46, p < 0.001, and lower benefit emotions, F = 16.61, p < 0.001. Pre-gameplay, there were no differences in challenge emotions, F = 1.17, p = 0.28, harm emotions, F < 1, or benefit emotions, F = 2.74, p = 0.10, and there were no differences between any emotion scales at baseline, F < 1. Overall, participants who received threat appraisal instructions reported more anxiety before the game, and reported more negative emotions and less positive emotions after the game.An analysis of simple main effects showed that threat appraisal groups had significantly higher threat emotion ratings than challenge groups pre-gameplay, F = 6.50, p < 0.01, ηp2 = 0.04, and benefit emotions, F = 5.33, p < 0.05, ηp2 = 0.04. There were also significant interaction effects of game content over time for challenge emotions, F = 3.77, p < 0.05, ηp2 = 0.03, and harm emotions, F = 5.45, p < 0.01, ηp2 = 0.04. An analysis of simple main effects showed that Mortal Kombat players had lower harm emotion ratings than Tetris players post-gameplay, F = 6.00, p < 0.05, and higher challenge emotion ratings post-gameplay, F = 10.16, p < 0.01. There were no significant differences in harm emotions at baseline, F < 1, or pre-gameplay, F < 1, or in challenge emotions at baseline, F = 2.76, p = 0.10, or pre-gameplay, F = 1.32, p = 0.25. Unexpectedly, Mortal Kombat players reported more positive emotions and less negative emotions than Tetris players after the game.There were significant main effects of game content on challenge emotions, F < 1, challenge, F = 3.17, p = 0.08, harm, F < 1, or benefit emotions, F < 1. There were also no three-way interactions over time for threat, F = 2.11, p = 0.12, challenge, F < 1, harm, F = 1.37, p = 0.25, or benefit emotions, F < 1.There was no appraisal × game content interactions for threat, t-tests showed that there was neither a significant difference between challenge  and threat instructions  on the number of matches won in Mortal Kombat, t(72) = −1.09, p = 0.28, nor a significant difference between challenge  and threat instructions  on the highest number of points achieved in Tetris, t(71) = 1.24, p = 0.22. Appraisal instructions did not influence game performance.Lastly, we predicted that threat instructions would result in lower game performance. Independent samples The primary purpose of the current study was to determine if playing video games can induce stress by manipulating video game instructions to evoke threat or challenge appraisals. We predicted that participants who received threat instructions would experience a cardiovascular stress response (higher blood pressure and lower heart rate variability) and would report more negative emotions after the game. We predicted that participants who received challenge instructions would not experience a cardiovascular stress response and would report more positive emotions after the game.We had mixed results in replicating previous findings using the Biopsychosocial Model of Challenge and Threat . As hypoCardiovascular outcomes were not consistent with previous findings using the model. Specifically, participants who received threat instructions had lower heart rate variability during the game as expected, but did not show increased blood pressure after gameplay. This contradicts previous research informed by the model, in which threat appraisals produced a cardiovascular stress response by increasing arousal and blood pressure, . In the The current study was the first to examine the model with video gameplay, and our cardiovascular findings may differ from previous studies because video games do not share the same characteristics as other mental stressors. Previous studies using the model have examined situational stimuli such as public speaking, word searches, exams, and social interviews . To evokMortal Kombat) and a puzzle video game (Tetris). There were significant differences in cardiovascular outcomes across different types of video games. For Tetris players, there were no changes in heart rate variability or blood pressure, but Mortal Kombat players had lower heart rate variability during gameplay and higher blood pressure after gameplay, indicating that Mortal Kombat players had a cardiovascular stress response. This supports previous video game studies in which similar fighting games increased arousal and blood pressure  and lower negative emotion ratings (frustration and anger) than Tetris players. These findings contradict previous research with video games, which have shown that puzzle games induce positive emotions such as relaxation (Emotion findings differed when comparing fighting and puzzle games. After gameplay, laxation  and fighlaxation . Our finlaxation . Individlaxation .Tetris players believed they would be more skilled at the video game than Mortal Kombat players, and had a greater decrease in perceived skill after gameplay. Thus, Tetris players seemed to perform worse than expected, and experienced lower perceived competence and higher levels of frustration after gameplay. This explanation is also supported by enjoyment ratings post-gameplay. Mortal Kombat players rated the game as more enjoyable, which may indicate that they had more perceived competence. Our findings demonstrate that video games with violent content can induce positive emotions, and create more positive emotional experiences than non-violent games depending on psychological factors and gameplay context. Although previous studies have demonstrated how violent games may or may not induce negative emotions (In the current study, secondary stress appraisal ratings may indicate that puzzle game players felt less fulfillment of their competence needs. Before the video game, emotions , very feemotions  as well emotions , which mThe current study is limited by assessing HPA activation with systolic and diastolic blood pressure measurements. Although previous studies using the Biopsychosocial Model of Challenge and Threat  have useMortal Kombat players succeeded in the game by winning individual matches, while Tetris players succeeded by continuously receiving points during a single level. Different in-game performance experiences could have affected participants’ perceived post-game appraisal of competence and post-game emotion ratings across game conditions. Furthermore, the current study did not measure the differences in gameplay attempts upon losing a match or level, which may have also affected perceived competence and emotional states.The use of pre-existing video games limits our ability to examine how specific factors in fighting games influence stress. We were unable to compare performance across game content and could not control for the potential effects of in-game differences in design, narrative, and mechanics on physiological and emotional stress outcomes. For example, the selected games in the current study had different requirements for in-game success. The current study advanced video game research by applying the Biopsychosocial Model of Challenge and Threat  to videoThe type of video game had an effect on stress outcomes, and we found that fighting game players showed a cardiovascular stress response after gameplay while puzzle game players did not. However, fighting game players also reported higher levels of positive emotions after gameplay. Previous studies with violent video games have only focused on negative emotion outcomes such as aggression , and vioThe application of the Biopsychosocial Model of Challenge and Threat  within tThis study was carried out in accordance with the recommendations of the Institutional Review Board committee and the Office of Research Compliance at The University of North Carolina at Charlotte with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Institutional Review Board committee.Frontiers in Psychology. AP contributed to the study design, data collection, data analysis, and drafting of the manuscript. PG contributed to the study design, data analysis, and revised the manuscript for important intellectual content. Both authors approved the final version of the manuscript for publication.All authors who meet authorship criteria are listed, and all authors certify that they have participated sufficiently to take public responsibility for the content in the submitted work, including participation in the concept, design, analysis, writing, or revision of the manuscript. Furthermore, each author certifies that this work has not been and will not be submitted to or published in any other publication before its appearance in 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.


Objective: Magnetic resonance imaging (MRI) and cardiac catheterization are diagnostic tools for right ventricle dysfunction (RVD), but those are expensive and often unavailable techniques. Thus, our objective was to identify clinical and/or echocardiographic variables capable of predicting a catheterization-based diagnosis of RVD.Design: This was cross-sectional, diagnostic test accuracy study, considering the catheterization-based diagnosis of RVD as the gold standard.Patients: Pediatric patients with non-repaired CHD with overload pressure were evaluated. Clinical variables , transthoracic echocardiography , and cardiac catheterization (pressures and right ventricle systolic work measurements) were obtained during the same hospitalization.Results: We included 253 patients with tetralogy of Fallot (39.9%), pulmonary atresia with ventricular septal defect (33.9%), type C Ebstein's anomaly (15.8%), or pulmonary stenosis (10.4%). Among clinical  and echocardiographic  variables, the Tei index (defined as the ratio of isovolumetric contraction time to ejection time) was the sole variable that exhibited high diagnostic capability, with 98.5% sensitivity, 97.4% specificity, 97.8% positive predictive value, and 98.3% negative predictive value, with 98.0% overall performance. Multivariate logistic regression confirmed that Tei index alone predicted the catheterization-based diagnosis of RVD.Conclusions: Tei index is the best parameter that can be employed for the non-invasive identification of RVD in patients with CHD. Currently, patients with congenital heart diseases (CHD) achieve more than 85% survival at 45 years of age, and this survival decreases according to the complexity of the cardiopathy . The majSome CHD, such as tetralogy of Fallot, pulmonary atresia with ventricular septal defect (PA+VSD), pulmonary valve stenosis (PVS), and type C Ebstein's anomaly , 5 shareMagnetic resonance imaging (MRI) is the best diagnostic tool for the evaluation of RVD, but it is expensive and not widely available. On the other hand, due to its capability for the evaluation of the morphology, functionality, and segmental pressures of the right ventricle, cardiac catheterization may be considered an equivalent of MRI . BecauseThis was a prospective study carried out at the CHD Service of the Hospital de Cardiología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, in Mexico City during the 2010–2015 period. The protocol was reviewed and approved by our institutional scientific and bioethics committee . During hospitalization, prior to the catheterization procedure, the researcher responsible for the investigation provided the assent and consent letters, and the parents of the patients provided their written informed consent for their child's participation in this study.The study population was composed of patients with a CHD and obstruction of the right ventricle output tract, such as tetralogy of Fallot, PA+VSD, PVS, and type C Ebstein's anomaly. They were inpatients of either sex, aged between 1 and 17 years, who were under preparation for total surgical repair. They were, during the same hospitalization, submitted to clinical evaluation and pre-surgical procedures including TTE and cardiac catheterization. These last procedures were performed by interventional cardiologists and echocardiographers certified in CHD and with ample experience in these procedures. Patients with non-programmed admission due to decompensation, with a prior non-palliative heart surgical procedure, with percutaneous valvuloplasty, or with coronary heart disease were excluded.2. This latter parameter was calculated by the formula proposed by Chemla et al. (before the outflow tract obstruction), instead of MPAP. In this calculation, we utilized the following formula: mean pressure of right ventricle at the infundibulum = (right ventricle systolic pressure at the infundibulum – right ventricle diastolic pressure at the infundibulum)/3 + right ventricle diastolic pressure at the infundibulum.Cardiac catheterization was performed via a femoral vein or, alternatively, by subclavian or jugular vein. RVD was considered to be present when all of the following variables coincided: (1) right ventricle systolic pressure  >30 mmHg; (2) right ventricle diastolic pressure  >12 mmHg, and (3) indexed right ventricle systolic work  < 4 kg/m/ma et al. , i.e., Rsystolic function were obtained and evaluated: (1) Indexed right ventricle diameter, expressed in millimeters (average of triplicate measurement) and considered abnormal when z-value was greater than 2 of reference values adjusted by body surface area (diastolic function were obtained: (1) The wave E′/A′ ratio, which was considered abnormal when <0.08. (2) Deceleration time, referred as abnormal if less than 23 m/s.Clinical evaluation was conducted by pediatric cardiologists not participating in this research. The clinical variables analyzed comprised the derangement of Ross functional class by ≥1 class during the previous year, and congestive data including hepatomegaly  or jugular vein distention above two thirds of the neck. TTE was carried out by experienced pediatric cardiologists or echocardiography cardiologists and according to international guidelines . The folace area . (2) Rigace area . (5) S' ace area . AdditioWe assessed the capability of clinical and echocardiographic variables to correctly diagnose RVD documented through cardiac catheterization. To this end, sensitivity, specificity, positive and negative predictive values, and overall performance were computed. Best cut-off point was evaluated through ROC curves. Multivariate logistic regression was employed to identify best predictor variables. Data was processed in Excel and SPSS v20 (IBM SPSS Statistics).A total of 253 patients  with CHD and obstruction of the right ventricle output tract were studied. The main characteristics of this population can be observed in Table When each potential predictor variable  was evaluated for its capability to predict RVD, it was evident that the Tei index possessed, by far, the highest overall accuracy (>95%) in any of the four CHD studied Table . This hir2 = 0.753.When TTE parameters were entered into a multivariate logistic regression analysis as continuous variables, the final regression model retained Tei index as the sole variable capable of predicting the probability of having RVD (pRVD), with high accuracy, excluding from the model all other variables . The final model was pRVD = −27.563 + 71.766 • Tei index, with a pseudo The frequency of RVD in patients with non-repaired CHD is unknown, but it has been estimated that, during the immediate postoperative period and subsequent follow-up, right ventricle dysfunction can be found in up to 25–30% of patients . In the Among the few studies that have assessed the value of TTE in CHD, Puchalski et al.  evaluateThe Tei index exhibited highest diagnostic accuracy across all types of CHD studied. Song et al.  demonstrr = 0.81) as compared with patients with tetralogy of Fallot (r = 0.65) (r = 0.80) with MRI-derived right ventricle ejection fraction in 36 adult patients submitted for evaluation of ischemia or viability. The authors suggested that this method could be utilized for the assessment of right ventricle function in the clinical setting, a suggestion that has been supported by others  . On the  = 0.65)  found thy others . In our The two echocardiographic measurements employed for evaluating right ventricle diastolic function exhibited lower diagnostic accuracy, probably because the major component of cardiopathies included in the study was obstructive in nature.In the present study, the two clinical variables analyzed  demonstrated low diagnostic accuracy in the majority of CHD. However, both clinical variables yielded a specificity of 100% among patients with type C Ebstein's anomaly. This may be explained because criteria for cardiac catheterization in Ebstein's anomaly comprises functional class derangement and low oxygen saturation (caused by a right-to-left shunt due to high pressures inside the right atrium) . BorgdorThe major limitation of our study was that the comparator for TTE was cardiac catheterization and not MRI, which at present is considered the gold standard for RVD evaluation. Likewise, we did not perform more sophisticated tests, such as strain rate or torsion, and in our RVD definition, we included RVSWi as indicator of contractile deficiency but, though reasonable, applicability of this parameter to CHD has not yet been corroborated. Conversely, advantages of our study included that the methodology employed warranted that both procedures (cardiac catheterization and TTE) were performed with a short lag time , and that patients were devoid of any ventricular damage secondary to surgical procedures, guaranteeing that the evaluation focused only on hemodynamic status conditioned by the CHD.In conclusion, the Tei index is a useful echocardiographic parameter for diagnosing RVD in pediatric population with CHD. This index is non-invasive, relatively easy to obtain, and can be repeated as many times as needed during the patient's follow-up. In countries where RMI and cardiac catheterization are not easily available, the Tei index may help clinicians to perform timely identification of RVD in order to modify treatment and achieve a better prognosis.All authors contributed substantially to the conception and design of the study, and to the critical review of the manuscript. LY-G performed the majority of echocardiographic evaluations. HM-G was the main individual responsible for the project and was involved in the full data collection and, along with MV, in data analysis and in drafting of the manuscript.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. The reviewer GJS and handling Editor declared their shared affiliation.