Factors Influencing the COVID-19 Vaccination Intentions in Parents for Their Children Aged 5~11: Korea, April 2022

Purpose@#This study aimed to investigate COVID-19 vaccination intentions in Korean parents for their children aged 5 to 11 years and the factors influencing them. @*Methods@#A cross-sectional online survey of 363 parents of children aged 5 to 11 years was conducted in Korea in April 2022. Data were analyzed using independent t-test, χ2-test, Fisher’s exact test, and hierarchical logistic regression analysis using SPSS/WIN 26.0 and MedCalc software version 20.113. @*Results@#Of 363 Korean parents with children aged 5 to 11, 42.4% intended to vaccinate their children. Significant factors influencing vaccination intention were the second or third birth order of children (OR = 3.45, 95% CI = 1.45~8.21), vaccine hesitancy-confidence (OR = 2.00, 95% CI = 1.51~2.65), vaccine hesitancy-collective responsibility (OR = 1.57, 95% CI: 1.10~2.25), and COVID-19 anxiety-avoidance (OR = 1.55, 95% CI = 1.13~2.11). @*Conclusion@#Findings suggest that COVID-19 vaccine campaigns based on reliable information and evidence from health authorities are needed to increase COVID-19 vaccination. Well-designed health communications for the target population may help to increase parental vaccine acceptance.

Intercoronary Communication between the Circumflex and Right Coronary Arteries Coexisted with Coronary Vasospasm

Intercoronary arterial connection between normal coronary arteries is a rare variant of coronary anatomy in which there is open-ended circulation. It is distinguished from collaterals seen in the occlusive coronary artery disease. We report a case of bidirectional intercoronary communication between the left circumflex artery and the right coronary artery without occlusive coronary artery disease, but with left anterior descending artery spasm.

Spontaneous Coronary Artery Dissection Mimicking Coronary Spasm Diagnosed by Intravascular Ultrasonography

Spontaneous coronary artery dissection (SCAD) is a rare and occasionally life-threatening cause of acute coronary syndrome. Patients may present with clinical scenarios ranging from angina pectoris to cardiogenic shock to sudden cardiac death, and it may be a potentially life-threatening condition if not recognized. However, its etiology, pathophysiology and optimal therapeutic strategies have not been well understood. SCAD is diagnosed on the basis of coronary angiography, but complementary techniques as such intravascular ultrasound (IVUS) and optical coherence tomography should be considered for diagnostic clarification where appropriate. Likewise, the selection of treatment strategy depends upon the clinical manifestation, location and the extent of dissection and amount of ischemic myocardium at risk. Herein, we present the case of a 35-year-old woman who presented with acute myocardial infarction. She was diagnosed by IVUS with spontaneous diffuse dissection of the left anterior descending artery without atheroma, treated with percutaneous coronary stenting, and had a favorable clinical course and was discharged on medical therapy.

Severe Pulmonary Hypertension in Primary Sjogren's Syndrome

A 65 year-old female with a history of xerostomia and xerophthalmia was presented with dyspnea on exertion (New York Heart Association class III). Echocardiography and cardiac catheterization demonstrated severe pulmonary hypertension (PH). Laboratory examinations showed positive anti-nuclear and anti-Ro/SS-A antibodies. Schirmer's test was positive and salivary gland scintigraphy revealed severely decreased tracer uptakes in both parotid and submandibular glands. By excluding other possible causes of PH during further examinations, she was diagnosed with severe PH associated with primary Sjogren's syndrome. Her dyspnea symptom was much improved with endothelin receptor antagonist and azathioprine.

Hypertension and Increased Left Ventricular End-diastolic Pressure Influence Arterial Stiffness

OBJECTIVE: There have been few studies regarding the relationship between arterial stiffness and left ventricular end-diastolic pressure (LVEDP). In the current study, we evaluated the relationship between the LVEDP and arterial stiffness in patients with hypertension (HTN). METHODS: Group I (n=34) included patients with a normal E/E' (8) without HTN, group III (n=20) included patients with a normal E/E' (8) with HTN. Aortic distensibility (AD) and the right brachial-ankle pulse wave velocity (baPWV) were measured. RESULTS: The mean age was 46.0+/-11.3 years. The mean value of AD was significantly lower in the group III compared to the group I. The group IV showed significantly lower AD compared to the group II. The group III demonstrated higher baPWV compared to the group I (1422+/-182 cm/sec vs. 1186+/-178 cm/sec, p<0.01), and the group IV showed higher baPWV compared to the group II (1456+/-228 vs. 1259+/-238 cm/sec, p<0.01). However, AD and baPWV were not significantly different between the group I and II, and between the group III and IV. The E/E' ratio showed a weak negative correlation with AD and a weak positive correlation with baPWV. CONCLUSION: Patients with hypertension showed a lower AD and a higher baPWV compared to those with normal blood pressure independent of the LVEDP. But the correlation between E/E' ratio and arterial stiffness suggests that a high LVEDP might not significantly influence arterial stiffness.

Pachydermoperiostosis Accompanied by Heart Failure

Pachydermoperiostosis or primary hypertrophic osteoarthropathy is an uncommon disease of acromegaloid facial feature, but characterized by unique phenotype (digital clubbing and pachydermia) and distinctive radiographic appearances like periostosis. We experienced a case with complete form of pachydermoperiostosis accompanied by heart failure. He presented with typical features consisting of clubbing with enlargement of the hand, thickening of facial skin and periosteal new bone formation involving lower leg. Echocardiography revealed severely decreased left ventricular systolic function. Treatment with medications resulted in an improvement of cardiac function and symptom. There is no previous report documenting pachydermoperiostosis accompanied by heart failure. We report that case for the first time.

Total Laparoscopic Liver Resection

PURPOSE: The aim of this study was to determine whether liver resection treated by using laparoscopy is equally safe for patients who have benign liver mass, hepatolithiasis, hepatocellular carcinoma (HCC), or metastatic liver cancer. METHODS: We performed our study in 32 patients with the following conditions: 17 patients with IHD stones, 7 with HCC, 1 with cholangiocarcinoma, and 7 patients who had colon cancer with liver metastasis. On a retrospective bases, these patients were investigated for clinical history, type of operation, time for the operation, hospital stay, and post operative complications. RESULTS: The target age range was from 37 to 80 years and the mean age was 61.2 years old. The percentage of patients over 60 years old was 68.7%. According to their past history, 8 patients had experienced an upper abdominal operation. In our study there were 9 cases of left hepatectomy (28.1%), 9 cases of left lateral segmentectomy (28.1%), 2 cases of sectionectomy, and 12 cases of wedgeresection. The average operation time was 364+/-148 mins, the average bleeding amount was 417 cc, and the average hospital stay was 13.2 days. There were 8 cases (25%) of postoperative complications developed (2 bile leak, 1 intrabdominal abscess, 1 acute renal failure, 2 wound infection). All cases were improved with conservative management. And there was one case of remnant IHD stone, which had surgical treat and one patient had peritoneal carcinomatosis, who had laparoscopic liver resection for HCC. CONCLUSION: Our study showed that laparoscopic liver resection has advantages; it is less painful, causes a small operative scar, a the short period of hospital stay and has cosmetic benefits. In the future, laparoscopic liver resection could be an important option for the treatment of hepatolithiasis and HCC through improved surgical instrument and skill of operation.

Clinical Significance of Left Ventricular Torsional Parameters during Supine Bicycle Cardiopulmonary Exercise Echocardiography

BACKGROUND: Left ventricular (LV) torsion plays an important role in both LV systolic and diastolic function. Notwithstanding the fact that speckle tracking imaging echocardiography (STI) is a validated method to measure LV torsion, few data regarding the clinical significance of LV torsional parameters using STI on exercise capacity during exercise echocardiography were reported. METHODS: Fifty four participants completed the supine bicycle cardiopulmonary exercise echocardiography under a symptom-limited protocol. LV torsion was defined as the net difference between LV peak apical rotation, and basal rotation divided by LV diastolic longitudinal length. LV basal, and apical short-axis rotations at each stage were analyzed by STI. RESULTS: LV torsion measurement was feasible in 43/54 (80%) at peak exercise. The LV torsions were increased during exercise, and even until the recovery. Peak twisting, and untwisting velocities were significantly increased during exercise, but were decreased at recovery. As expected, baseline torsion was positively correlated with LV ejection fraction and baseline apical peak untwisting velocity has correlation with E/E' (r=0.50, p<0.01 and r=0.30, p<0.05, respectively). Interestingly, apical peak twisting velocity at peak exercise was significantly correlated with maximal O2 consumption and VO2 interval change (r=0.50, p<0.01 and r=0.33, p<0.05, respectively). CONCLUSION: It was feasible to measure LV torsion by STI at every step during exercise echocardiography, although the feasibility was relatively low at peak exercise. LV torsional parameters during exercise showed significant relations with exercise capacity as well as LV systolic and diastolic functions.

FAS (Fatty acid synthase) expression in breast cancer / 한국유방암학회지

PURPOSE: Fatty acid synthase (FAS) is a multi-enzyme molecule that plays a role in the de novo biosynthesis of fatty acids. FAS is expressed at low levels in most normal human tissues because, cells preferentially utilize circulating lipids for the synthesis of new structural lipids. Recent studies have demonstrated that high levels of FAS occur in a subset of human cancers (such as breast, ovary, and prostate cancer etc) and these high FAS levels are associated with a poor prognosis. The aim of this study was to investigate the expression of FAS in breast cancer and to examine the relationship between FAS and the clinicopathological data. METHODS: We reviewed clinical profiles [clinical data and short term outcome (recurrence)] of 67 breast cancer patients by reviewing their medical records. The average followed-up period was 22.6 month. FAS expressions were evaluated by immunohistochemistry on the formalin-fixed paraffin-embedded tissues. RESULTS: FAS expression of breast cancer was nonspecifically high, but there was no statistical importance between the FAS expression, the clinicopathological data and the short term recurrence (p > 0.05). CONCLUSION: The overexpression of FAS in breast cancer patients may not be a reliable marker for a poor prognosis. However, further studies are required in order to define the biological significance and the specific role of FAS in breast cancer development, growth, and invasion. Also, inhibition of FAS may be a target treatment for breast cancer.

FAS (Fatty acid synthase) expression in breast cancer / 한국유방암학회지

PURPOSE: Fatty acid synthase (FAS) is a multi-enzyme molecule that plays a role in the de novo biosynthesis of fatty acids. FAS is expressed at low levels in most normal human tissues because, cells preferentially utilize circulating lipids for the synthesis of new structural lipids. Recent studies have demonstrated that high levels of FAS occur in a subset of human cancers (such as breast, ovary, and prostate cancer etc) and these high FAS levels are associated with a poor prognosis. The aim of this study was to investigate the expression of FAS in breast cancer and to examine the relationship between FAS and the clinicopathological data. METHODS: We reviewed clinical profiles [clinical data and short term outcome (recurrence)] of 67 breast cancer patients by reviewing their medical records. The average followed-up period was 22.6 month. FAS expressions were evaluated by immunohistochemistry on the formalin-fixed paraffin-embedded tissues. RESULTS: FAS expression of breast cancer was nonspecifically high, but there was no statistical importance between the FAS expression, the clinicopathological data and the short term recurrence (p > 0.05). CONCLUSION: The overexpression of FAS in breast cancer patients may not be a reliable marker for a poor prognosis. However, further studies are required in order to define the biological significance and the specific role of FAS in breast cancer development, growth, and invasion. Also, inhibition of FAS may be a target treatment for breast cancer.

Granulomatous mastitis / 한국유방암학회지

Granulomatous Mastitis (GM) is a rare chronic inflammatory lesion of the breast that clinically simulate carcinoma. The purpose of this report is to review the clinicopathological features of this clinical entity in a series of 5 cases that were diagnosed at our institute. Mammography, ultrasonography, and fine needle aspiration were performed in all cases. The treatment of choice for granulomatous mastitis is unclear. Of the 5 cases, one case underwent steroid therapy, two cases underwent anti-tuberculosis medication, and the others underwent only excision. There were no complications for the 5 cases during the follow-up periods. Therefore, the diagnosis and treatment of granulomatous mastitis should be determined on a case by case basis, by the clinician considering the various case results that have been reported on.

Changes in plasma level of B-type natriuretic peptide and myocardial performance index according to clinical improvement in patients with heart failure / 대한내과학회지

BACKGROUN: B-type natriuretic peptide (BNP) is a cardiac neurohormone secreted from ventricles as a response to ventricular volume expansion and pressure overload. Myocardial performance index (MPI) reflects cardiac systolic and diastolic function and increase in the patients with congestive heart failure (CHF). The purpose of this study was to evaluate the correlation of clinical status of CHF, BNP level, and MPI. METHODS: We followed 30 patients (mean age: 64 +/- 13) admitted with symptomatic New York Heart Association (NYHA) class III to IV CHF. Medical treatment was done. Biochemical study including BNP level and evaluation of left ventricular (LV) function including MPI by echocardiography were performed at admission and 2 months later. RESULTS: Mean BNP level increased to 488.64 +/- 519.85 pg/mL at admission with symptomatic CHF and significantly decreased to 319.56 +/- 385.39 pg/mL (p-value: 0.014) after clinical improvement. Mean MPI tended to decrease from 0.62 +/- 0.37 to 0.45 +/- 0.26. Readmission rate in 4 months was high in the patients with small decrease in BNP level. At admission, the patients with symptomatic CHF showed increased MPI despite of normal LV systolic function and tendency to decrease in MPI after clinical improvement. CONCLUSION: Increased BNP level and MPI of patients admitted with symptomatic CHF decreased with clinical improvement. The results suggest that BNP level and MPI might be useful to guide treatment of patients with CHF and changes in BNP level during treatment are predictors of early readmission.

The Effects of Platelet-Derived Growth Factor Inhibitor(Trapidil) on Intimal Hyperplasia Following Coronary Stenting: Assessed by Intravascular Ultrasound

BACKGROUND AND OBJECTIVES: Platelet-derived growth factor (PDGF) seems to be one of the most powerful factors associated with the proliferative process that occurs after percutaneous transluminal coronary angioplasty (PTCA), and leads to restenosis. Trapidil (Triazolopyrimidine), a potent inhibitor of PDGF, was shown to decrease restenosis after experimental balloon angioplasty. The aim of this study was to assess the effects of trapidil, on intimal hyperplasia, following coronary artery stenting, using volumetric intravascular ultrasound (IVUS) analysis. SUBJECTS AND METHODS: The patients were divided in 2 groups; Group I (n=14, age=53+/-8, male=11) received trapidil (600 mg) for 6 months, aspirin (200 mg) indefinitely and ticlopidine (250 mg) for 4 weeks, Group 2 (n=15, age=55+/-2, male=9) received aspirin (200mg) indefinitely and ticlopidine (500 mg) for 4 weeks, starting at least 3 days before the angioplasty. A serial IVUS study was performed post-stenting, with a 6 month follow up period. Both the stent (SA) and lumen areas (LA) were measured, and the stent (SV), lumen (LV) and intimal hyperplasia volumes (IHV) were calculated using Simpson's rule. RESULTS: The reference (RD), pre minimal luminal (MLD) and post minimal luminal diameters, as measured by quantitative coronary angiographic analysis (QCA), were not different between the two groups. Using serial IVUS measurements, SV and LV were not different between the two groups. Also, the IHV was not different between the two groups (51.9+/-26.1 and 61.3+/-25.3 mm3, respectively, p=NS). CONCLUSION: Trapidil failed to reduce intimal hyperplasia following coronary stenting compared with the controls.

Evaluation of Sympathetic Reinnervation Using 123I-MIBG Scintigraphy in Cardiac Transplants

BACKGROUND AND OBJECTIVES: It is known that sympathetic reinnervation, following a heart transplantation, increases with time. 123I metaiodobenzylguanidine (123I-MIBG) is taken up by myocardial sympathetic neurons in a manner similar to norepinephrine (NE), and is used as an imaging agent. The purpose of this study was to evaluate cardiac sympathetic reinnervation, following an orthotopic heart transplantation, using 123I-MIBG scintigraphy. SUBJECTS AND METHODS: Twenty four 123I-MIBG images of the chest were taken in 15 patients (10 males, 5 females, mean age: 35+/-13 years), 1 to 48 (mean 10.8+/-11.9) months after a transplantation. Two healthy adults were studied as normal controls. The 123I-MIBG images were acquired at 15 minutes, and 4 and 24 hours, after an intravenous injection of 185 MBq 123I-MIBG. To quantitate the degree of myocardial uptake of the MIBG, the heart to mediastinal ratio (HMR) was measured. In nine patients, the 123I-MIBG scintigraphy was repeated one year later. RESULTS: The HMRs of the 4 and 24 hour images (1.26+/-0.23, 1.06+/-0.10, respectively) were lower than those of the 15 minute images (1.48+/-0.28). Twelve subjects, 1 to 12 months after the transplantation, showed no visible myocardial activities, but 12 subjects, 13 to 48 (28.6+/-12.8) months after the transplantation, showed visible myocardial 123I-MIBG uptakes (HMR: 1.65+/-0.21). The HMRs were high in normal controls (mean 2.84). One-year follow up scintigraphy showed increased HMRs compared with those taken immediately postoperatively (1.40+/-0.31 to 1.61+/-0.16, p<0.05). CONCLUSION: Partial sympathetic late reinnervation can occur one year after a transplantation.

Clinical Experience of Cutting Balloon Angioplasty for in Stent Restenosis

BACKGROUND AND OBJECTIVES: A cutting balloon (CB) is a balloon catheter with 3 or 4 metal blades on its surface used for making controlled endovascular surgical incisions and promising minimal intimal injury. Some reports suggest advantages of the use of CB in the treatment of in-stent restenosis (ISR). The purpose of this study was to report the clinical experience of the use of CB for ISR. SUBJECTS AND METHODS: 28 patients were enrolled in this study. Angiographic success (defined by 40% residual stenosis), in-hospital, 30 days and 6 months clinical outcomes were evaluated. RESULTS: Angiographic success was 92.9% (26/28). The number of inflations and maximal inflation pressure were 2.8+/-0.9 and 10.1+/-1.3 ATM, respectively. The balloon/artery (B/A) ratio was 1.1+/-0.2. There was a case of stent insertion for treating type D dissection and a case of rotational atherectomy for suboptimal result after CB angioplasty. 25 cases underwent analysis through 6 months of clinical follow-up. During the 6-month clinical follow-up, 4 cases of re-PTCA were documented, while MACE during in-hospital time and the subsequent 30 days was 0%. CONCLUSION: Our experience demonstrated that CB can be performed safely and effectively in coronary ISR. Further clinical and angiographic effectiveness are warranted in a large-scale clinical trial.

Esophageal Leiomyomatosis in a patient with Alport Syndrome / 대한흉부외과학회지

A-13-urar-old with a history of Alport syndrome had been suffering from progressive dysphagia and postprandial vomiting for over 7 years. Exophagogram and manoemtric studies were consistent with achalasia. Barum study demonstrated marked esophageal dilatation and smooth tapered narrowing of the distal esophagus. However in spite of the medical treatment including the injection of the distal esophagus. However in spite of the medical treatment including the injection of botulinum toxin at the lesion site using an endoscope symptom did not improved and he suffered growth failure and malnutrition. Esophagectomy and esophagogastrostomy were performed to relieve the dysphagia. A firm circumferential intramural mass about 7x5x5 cm was found in the distal esophagus. The lumen of the esophagus was markedly dilated and esophageal wall was hypertrophied. Histologic examination of the neoplasm revealed a rather ill defined tumor tissue consisting of interlacing or whirling spindle cells without significant mitosis and esophageal leiomyo-matosis was confirmed. The patient was discharged uneventfully.

Clinical esxperiences of Carotid Endarterectomy for Carotid Stenosis / 대한흉부외과학회지

BACKGROUND: The purpose of carotid endarterectomy is to prevent stroke regardless of past neurologic events. Major concern in the carotid endarterectomy is the inadequate blood flow of ipsilateral hemisphere during clamping of the carotid artery. It is well known that internal carotid artery back pressure means collateral cerebral blood flow. Our study is intended to determine the guideline of shunt placement according to the carotid back pressure and electroencephalographic finding. MATERIAL AND METHOD: The study population comprised of 16 consecutive patients who underwent carotid endarterectomy for carotid stenosis in our institution between from February 1996 to March 1999. There were 14 men and 2 women between the ages of 56 and 78 years(mean age 66.25+/-6.53 years). The carotid stenosis in the operative site was ranged from 61% to 95%(mean 73.8+/-12.33%) and the mean carotid stenosis of the contralateral side was 60.99+/-25.03%. During the operation, electroencephalographic monitoring was taken in all cases. The internal carotid artery back pressure was measured to estimate the collateral cerebral blood flow, and in all patients with back pressure below 40 mmHg(11 patients) and patients with complete occulusion of contralateral carotid artery(2 patients), an internal shunt was installed. RESULT: One postoperative death occurred in a patient with large evolving cerebral infarction and severe ipsilateral carotid stenosis, who underwent emergent carotid endarterectomy. The cause of death was hemorrhagic infarction in the corresponding cerebral territory. We observed that immediate operation after a major stroke negatively influenced the postoperative outcome. No intraoperative ischemic neurologic complication developed. During the follow-up upto now(mean follow-up 21.5+/-11.85 months), there has been no early or late recurrence of stroke except one patient ,in whom cerebral infarction developed in the contralateral side on the first postoperative day. CONCLUSION: At least 4-6 weeks stabilization after a stroke is recommended for surgical management. The carotid endarterectomy is an effective surgical intervention for prevention of anticipated stroke and can be performed safely if an internal shunt is used in patients whose internal carotid arterial back pressure is below 40 mmHg.

Decision of Shunt Insertion Based on Electroencephalography and Stump Pressure During Carotid Endarterectomy

BACKGROUND: Carotid endarterectomy (CEA) is an effective treatment for the prevention of stroke in patients with high grade carotid stenosis. Electroencephalographic (EEG) monitoring and measurement of stump pressure are the most widely used methods for assessing the risk of cerebral ischemia during CEA. We designed this study to assess the usefulness of EEG and stump pressure for shunt insertion during CEA. METHODS: Nineteen patients were enrolled from January, 1996 to April, 1999. We calculated the percent of carotid stenosis in the patients by the NASCET (North American Symptomatic Carotid Endarterectomy Trial) criteria. The inclusion criteria of the CEA were high grade stenosis (>70%), or moderate stenosis (>50%) with ulcerated plaque. Intra-operative monitoring by using stump pres-sure, and an EEG was performed in 19 operations. RESULTS: The number of patients with asymptomatic and sympto-matic carotid stenosis were 6 and 13 respectively. Shunt during the operations was used in 12 patients; nine had both significant EEG changes and low stump pressures, two had only low stump pressure, one patient had only a significant EEG change. The peri-operative complications of mortality and stroke were found in one case. In the other patients, there no stroke recurrences during the mean follow-up period of 24 months. CONCLUSIONS: EEG and stump pressure may be useful in deciding shunt insertion during CEA for detecting ischemic changes.

Stenting of an Anomalous Coronary Artery in Acute Myocardial Infarction

Single coronary artery is rare and the application of coronary angioplasty to these arteies presents unique technical challenge. As technical advances in the guiding catheter and balloon system occur, more challenging lesions including anomalous coronary artery are able to be treated. Correct guiding catheter selection is important to ensure adequate access to the anomalous vessel and provide support to cross the lesion. This report describes successful angioplasty with stent in right coronary artery of single ostium coronary anomaly in a patient presenting with an acute myocardial infaction.

First Successful Dynamic Cardiomyoplasty in Korea / 대한흉부외과학회지

A 25-year-old man with viral cardiomyopathy and chronic active hepatitis successfully underwent dynamic cardiomyoplasty for the first time in Korea on July 30, 1996. The patient had been intermittently dyspneic for 5 years and was admitted to our center twice because of heart failure. For the past 2 years, he was NYHA functional class III status with a left ventricular ejection fraction (LVEF) of around 30%. The patient was born with scoliosis and showed a short stature. The liver function showed elevated liver enzymes, and hepatitis B antigen was positive. The liver biopsy revealed chronic active hepatitis. The preoperative echocardiogram showed decreased left ventricular function with grade II mitral and grade II tricuspid regurgitation with dilated left and right atrium. Recently his symptoms worsened and we decided to perform a dynamic cardiomyoplasty. The left latissmus dorsi muscle (LDM) was mobilized and tested with lead placement on his right lateral decubitus position. The patient was positioned into supine and, after median sternotomy, the heart was wrapped with the mobilized muscle. The Russian made cardiomyostimulator (EKS-445) and leads (Myocardial PEMB for heart and PEMP-1 for LDM) were used. The total operation time was 8 hours and there were no perioperative episodes. Postoperatively the LDM had been trained for a 10 week period and currently the stimulation ratio is maintained at 1:4. The postoperative LVEF did not increase with the value of 30-35%. However, the patient feels better postoperatively with slightly increased activity.