Improvement of Constipation Symptoms in an Older Adult Patient by Defecation Care Based on Using a Handheld Ultrasound Device in Home Care Settings: A Case Report.

BACKGROUND: Although previous studies have demonstrated the ability of ultrasound to detect stool in the colon and rectum, the clinical utility of evaluating constipation via ultrasonic imaging by nurses has not been determined. In this case report, we observed fecal retention, assessed the presence of constipation, and performed defecation care in an older adult patient in a home care setting in a city near the metropolitan area in Japan. CASE: An 85-year-old male with advanced stage prostate cancer and multiple metastases was diagnosed with fecal impaction via digital rectal examination and evaluation of stool consistency. He was managed by regular digital evacuation of stool, but ultrasonic imaging indicated constipation with fecal retention in both the rectum and the colon despite this bowel evacuation program. When faced with this situation, we advocate a bowel management program that considers both intestinal elimination dysfunction and fecal transport dysfunction. Based on ultrasonic imaging, stool consistency was altered by promoting water intake, and we promoted self-defecation by asking the patient to attempt to move his bowels (regardless of cues to defecation) by sitting on the toilet every morning. As a result, the number of weekly enemas and digital dis-impaction episodes decreased while the number of spontaneous defecations increased. CONCLUSION: This case report demonstrated that ultrasonography improved bowel management in this patient with clinically severe chronic constipation.

Sudden cardiac arrest immediately after stent graft deployment during treatment of iliac aneurysm with iliocaval fistula.

An 84-year-old woman with heaviness of the right lower extremity had an iliocaval fistula related to a right internal iliac aneurysm. Immediately after deployment of an endovascular device, cardiac arrest occurred because of severely decreased sympathetic activity. After surgery, the patient recovered well and has been followed up with exclusion of the arteriovenous fistula and resolution of the type II endoleak. Endovascular treatment for large arteriovenous fistulas induces rapid closure of the fistula together with restoration of blood supply to the lower extremity. Markedly deactivated sympathetic nerve traffic could result in a critical hemodynamic status in association with endograft deployment.

Outcomes of Balloon Kyphoplasty for Vertebral Compression Fractures in Patients with Diffuse Idiopathic Skeletal Hyperostosis at the Distal End or Adjacent Vertebra of the Fused Segments.

STUDY DESIGN: A retrospective cohort study. PURPOSE: To investigate the outcomes of balloon kyphoplasty (BKP) for vertebral compression fractures (VCFs) at the distal end or adjacent vertebra of the fused segments in patients with diffuse idiopathic skeletal hyperostosis (DISH). OVERVIEW OF LITERATURE: Vertebral fractures in the midportion of the fused segments in patients with DISH are generally unstable; thus, immobilization is recommended. However, VCFs classified as type A in the AO classification are observed at the distal end and adjacent vertebra of the fused segments, and treatment strategies for VCFs associated with DISH remain controversial. METHODS: The outcomes of 72 patients who underwent BKP for VCFs between 2015 and 2021 were retrospectively investigated. Patients with DISH were assigned to group D (n=21), whereas those without DISH were assigned to group ND (n=51). Back pain, incidence of subsequent adjacent fractures, reoperation rates, and local kyphosis were statistically analyzed. RESULTS: VCFs in group D occurred at the distal end or adjacent vertebra of the fused segments, and no fractures occurred in the midportion of the fused segment. Back pain improved in both groups, with no significant differences between them. Subsequent adjacent fractures were observed in three of the 21 patients in group D and 11 of the 51 patients in group ND, with no significant difference between them. Reoperation was performed in one patient each in groups D and ND, with no significant difference between the groups. Postoperatively, local kyphosis progressed significantly in group D. CONCLUSIONS: Although local kyphosis is more advanced in patients with DISH, BKP is effective for VCFs at the distal end or adjacent vertebra of the fused segments and may be useful in older patients with high complication rates.

Prognosis of home-cared or hospital-treated acute fever in older adults: A prospective multicenter case-control study.

AIMS: This study aimed to investigate the differences in the prognosis of older patients who received home care or hospitalized care to treat acute fever in Japan. METHODS: This prospective case-control study screened 192 registered acutely pyrexic older patients who received home care at 10 medical institutions in Japan, and enrolled 15 and 30 patients who were treated in the hospital (hospitalized group) and at home (home-care group), respectively, matched for fever and the physical conditions before fever onset. Intergroup differences in the 90-day mortality from fever onset and changes in patients' disability and dementia from the pre-fever to 90 days post-fever onset were determined. RESULTS: No significant intergroup difference in the 90-day mortality rate was detected (26.7% vs 13.3% for hospitalized and home-care groups, respectively, P = 0.41). Disability tended to worsen in the hospitalized group compared with the home-care group (54.5% vs 23.1%, respectively, P = 0.06), whereas dementia significantly worsened in the hospitalized group compared with the home-care group (45.5% vs 3.8%, respectively, P = 0.02). CONCLUSIONS: Home care confers a better prognosis for treating acute fever in older people whose daily functions have deteriorated enough to necessitate regular home care. This study assists those people in making informed choices about where to receive treatment for acute fever. Geriatr Gerontol Int 2023; 23: 355-361.

Negative Effects of Diffuse Idiopathic Skeletal Hyperostosis on Bone Fusion after Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: This study adopted a retrospective cohort study design. PURPOSE: This study aimed to clarify the influence of diffuse idiopathic skeletal hyperostosis (DISH) on bone fusion after transforaminal lumbar interbody fusion (TLIF). OVERVIEW OF LITERATURE: The negative effects of DISH on lumbar degenerative diseases have been reported, and DISH may be involved in the onset and severity of lumbar spinal canal stenosis. Patients with DISH have significantly more reoperations after posterior lumbar fusion, including TLIF. However, the effects of DISH on bone fusion after TLIF have not been reported. METHODS: The medical records of patients with intervertebral TLIF from 2012 to 2018 were retrospectively examined. The patients were divided into those with fusion and those with pseudoarthrosis, and the following data were compared: age, sex, DISH, diabetes mellitus, smoking, drinking, albumin levels, body mass index ≥30 kg/m2, and L5/S fixation. Statistical analyses were performed using regression models. RESULTS: In this study, 180 patients (78.6%) had fusion and 49 patients (21.4%) had pseudoarthrosis. The number of patients with DISH was significantly higher in the pseudoarthrosis group than in the fusion group (36.7% and 21.7%, respectively; univariate p=0.031, multivariate p =0.019). No significant differences in age, sex, diabetes mellitus, smoking, drinking, albumin levels, body mass index ≥30 kg/m2, and L5/S fixation were observed between the two groups. The risk factors for bone fusion were statistically analyzed in 57 patients with DISH. DISH with a caudal end below Th11 was an independent risk factor for pseudoarthrosis (univariate p=0.011, multivariate p=0.033). CONCLUSIONS: DISH is an independent risk factor for pseudoarthrosis after one intervertebral TLIF, and DISH with a caudal end below Th11 is associated with a higher risk of pseudoarthrosis than DISH without a caudal end below Th11.

Isolation of a small vasohibin-binding protein (SVBP) and its role in vasohibin secretion.

Upon stimulation with angiogenic factors, vascular endothelial cells (ECs) secrete a negative-feedback regulator of angiogenesis, vasohibin-1 (VASH1). Because VASH1 lacks a classical signal sequence, it is not clear how ECs secrete VASH1. We isolated a small vasohibin-binding protein (SVBP) composed of 66 amino acids. The level of Svbp mRNA was relatively high in the bone marrow, spleen and testes of mice. In cultured ECs, Vash1 mRNA was induced by VEGF, and Svbp mRNA was expressed constitutively. The interaction between VASH1 and SVBP was confirmed using the BIAcore system and immunoprecipitation analysis. Immunocytochemical analysis revealed that SVBP colocalized with VASH1 in ECs. In polarized epithelial cells, SVBP accumulated on the apical side, whereas VASH1 was present throughout the cells and partially colocalized with SVBP. Transfection of SVBP enhanced VASH1 secretion, whereas knockdown of endogenous SVBP markedly reduced VASH1 secretion. SVBP increased the solubility of VASH1 protein in detergent solution and inhibited the ubiquitylation of VASH1 protein. Moreover, co-transfection of SVBP significantly augmented the inhibitory effect of VASH1 on EC migration. These results indicate that SVBP acts as a secretory chaperone for VASH1 and contributes to the anti-angiogenic activity of VASH1.

Prevention of alveolar air leakage after video-assisted thoracic surgery: comparison of the efficacy of methods involving the use of fibrin glue.

BACKGROUND: The aim of this study was to evaluate the appropriate condition of use of the fibrin glue plus polyglycolic acid (PGA) sheet combination to obtain the optimal sealing effect. METHODS: 126 consecutive patients underwent video-assisted thoracic surgery (VATS) were divided into groups as follows: fibrin glue sprayed on the PGA sheet placed over the pleural defect (Method I); fibrinogen and thrombin solutions sprayed separately on the PGA sheet soaked in thrombin and placed over the pleural defect after rubbing of fibrinogen solution on the area (Method II); fibrin glue sprayed on the PGA sheet placed over the pleural defect after rubbing of fibrinogen solution on the area (Method III). Method II and Method III were also examined in an animal model. RESULTS: Postoperative air leakage was more effectively prevented by Method III than by the other two methods (p < 0.05). In the experimental study, a significantly higher seal-breaking pressure was obtained for Method III than for Method II (p < 0.05). CONCLUSION: Method III was the most effective for preventing alveolar air leakage.

What Should Be Considered When Evaluating the Quality of Home Care? A Survey of Expert Opinions on the Evaluation of the Quality of Home Care in Japan.

Intending to obtain scientific evidence to use in developing indicators for evaluating the quality of home care, we surveyed doctors, nurses, and other home care professionals to determine the points they consider to be essential in evaluating home care. We investigated all 901 clinics registered to the National Association of Medical Institutions Supporting Home Care and a random sample of 600 Visiting Nurse Service stations registered to the National Association for Visiting Nurse Service in Japan. A total of 539 questionnaire responses were received (response rate: 35.9%). In this study, a factor analysis revealed four factors to be considered when evaluating the quality of home care: (1) patients' and family members' level of satisfaction, (2) home care process, (3) structure of home care, and (4) medical outcomes. The factor of the satisfaction of patients and family members identified in the present study was not considered in previous studies for evaluating the quality of care in Japan. Satisfaction is the point of difference in goals between hospital-based care and home care, and it requires different measurement indicators. Home care professionals expect to help relieve the physical and psychological burden felt by the patient and their family. Thus, on the evaluation indicators of quality of home care, their perspectives from the present study are valuable.

Endogenous angiogenesis inhibitor vasohibin1 exhibits broad-spectrum antilymphangiogenic activity and suppresses lymph node metastasis.

During cancer progression, the angiogenesis that occurs is involved in tumor growth and hematogenous-distant metastasis, whereas lymphangiogenesis is involved in regional lymph node metastasis. Angiogenesis is counterregulated by various endogenous inhibitors; however, little is known about endogenous inhibitors of lymphangiogenesis. We recently isolated vasohibin1 as an angiogenesis inhibitor intrinsic to the endothelium and further demonstrated its anticancer activity through angiogenesis inhibition. Here, we examined the effect of vasohibin1 on lymphangiogenesis. Vasohibin1 exhibited broad-spectrum antilymphangiogenic activity in the mouse cornea induced by factors including VEGF-A, VEGF-C, FGF2, and PDGF-BB. We then inoculated highly lymph node-metastatic cancer cells into mice and examined the effect of vasohibin1 on lymph node metastasis. Tail-vein injection of adenovirus containing the human vasohibin1 gene inhibited tumor lymphangiogenesis and regional lymph node metastasis. Moreover, local injection of recombinant vasohibin1 inhibited lymph node metastasis. These results suggest vasohibin1 to be the first known intrinsic factor having broad-spectrum antilymphangiogenic activity and indicate that it suppresses lymph node metastasis.

Distinctive localization and opposed roles of vasohibin-1 and vasohibin-2 in the regulation of angiogenesis.

We recently isolated a novel angiogenesis inhibitor, vasohibin-1, and its homologue, vasohibin-2. In this study we characterize the role of these 2 molecules in the regulation of angiogenesis. In a mouse model of subcutaneous angiogenesis, the expression of endogenous vasohibin-1 was low in proliferating ECs at the sprouting front but high in nonproliferating endothelial cells (ECs) in the termination zone. In contrast, endogenous vasohibin-2 was preferentially expressed in mononuclear cells mobilized from bone marrow that infiltrated the sprouting front. When applied exogenously, vasohibin-1 inhibited angiogenesis at the sprouting front where endogenous vasohibin-1 was scarce but did not influence vascularity in the termination zone where endogenous vasohibin-1 was enriched. Exogenous vasohibin-2 prevented the termination of angiogenesis in the termination zone and increased vascularity in this region. Angiogenesis was persistent in the termination zone in the vasohibin-1 knockout mice, whereas angiogenesis was deficient at the sprouting front in the vasohibin-2 knockout mice. Supplementation of deficient proteins normalized the abnormal patterns of angiogenesis in the vasohibin knockout mice. These results indicate that vasohibin-1 is expressed in ECs in the termination zone to halt angiogenesis, whereas vasohibin-2 is expressed in infiltrating mononuclear cells in the sprouting front to promote angiogenesis.

Kinematic evaluation of the adjacent segments after lumbar instrumented surgery: a comparison between rigid fusion and dynamic non-fusion stabilization.

The aim of the current study was to evaluate changes in lumbar kinematics after lumbar monosegmental instrumented surgery with rigid fusion and dynamic non-fusion stabilization. A total of 77 lumbar spinal stenosis patients with L4 degenerative spondylolisthesis underwent L4-5 monosegmental posterior instrumented surgery. Of these, 36 patients were treated with rigid fusion (transforaminal lumbar interbody fusion) and 41 with dynamic stabilization [segmental spinal correction system (SSCS)]. Lumbar kinematics was evaluated with functional radiographs preoperatively and at final follow-up postoperatively. We defined the contribution of each segmental mobility to the total lumbar mobility as the percent segmental mobility [(sagittal angular motion of each segment in degrees)/(total sagittal angular motion in degrees) × 100]. Magnetic resonance imaging was performed on all patients preoperatively and at final follow-up postoperatively. The discs were classified into five grades based on the previously reported system. We defined the progress of disc degeneration as (grade at final follow-up) - (grade at preoperatively). No significant kinematical differences were shown at any of the lumbar segments preoperatively; however, significant differences were observed at the L2-3, L4-5, and L5-S1 segments postoperatively between the groups. At final follow-up, all of the lumbar segments with rigid fusion demonstrated significantly greater disc degeneration than those with dynamic stabilization. Our results suggest that the SSCS preserved 14% of the kinematical operations at the instrumented segment. The SSCS may prevent excessive effects on adjacent segmental kinematics and may prevent the incidence of adjacent segment disorder.

Age, gender, will, and use of home-visit nursing care are critical factors in home care for malignant diseases; a retrospective study involving 346 patients in Japan.

BACKGROUND: We aimed to clarify the factors affecting outcomes of home care for patients with malignant diseases. METHODS: Of 607 patients who were treated in 10 clinics specialized in home care between January and December 2007 at Chiba, Fukuoka, Iwate, Kagoshima, Tochigi and Tokyo prefectures across Japan, 346 (57%; 145 men and 201 women) had malignant diseases. We collected information on medical and social backgrounds, details of home care, and its outcomes based on their medical records. RESULTS: Median age of the patients was 77 years (range, 11-102), and 335 patients were economically self-sufficient. Their general condition was poor; advanced cancer (n = 308), performance status of 3-4 (n = 261), and dementia (n = 121). At the beginning of home care, 143 patients and 174 family members expressed their wish to die at home. All the patients received supportive treatments including fluid replacement and oxygenation. Median duration of home care was 47 days (range, 0-2,712). 224 patients died at home. For the remaining 122, home care was terminated due to complications (n = 109), change of attending physicians (n = 8), and others (n = 5). The factors which inhibited the continuity of home care were the non-use of home-visit nursing care (hazard ratio [HR] = 1.78, 95% confidence interval [CI]: 1.05-3.00, p = 0.03), the fact that the patients themselves do not wish to die at home (HR = 1.83, CI: 1.09-3.07, p = 0.02), women (HR = 1.81, CI: 1.11-2.94, p = 0.02), and age (HR = 0.98, CI: 0.97-1.00, p = 0.02). CONCLUSIONS: Continuation of home care is influenced by patients' age, gender, will, and use of home-visit nursing.

Feasibility of the constipation point-of-care ultrasound educational program in observing fecal retention in the colorectum: A descriptive study.

AIM: Nurses have difficulty assessing the type of constipation by ordinal assessment methods and may therefore struggle to select an appropriate defecation care. Although previous studies described the safety and effectiveness of defecation care based on ultrasonographic observations in the colorectum, no standardized educational program has been established. This study aimed to determine the feasibility of the constipation point-of-care ultrasound (POCUS) educational program regarding the use of ultrasonography as an assessment tool to determine different types of constipation. METHODS: This descriptive study was conducted for visiting nurses working in Japan. The constipation POCUS educational program that nurses can learn in as short as 7 days comprised four elements: E-learning, a hands-on seminar, self-learning, and objective structured clinical examinations (OSCEs). The nurses were asked to complete a questionnaire regarding the education materials. OSCEs were used to assess the participants' skills in assessing patients based on the use of ultrasound observation in the colorectum. RESULTS: Of the 44 participants who enrolled, 40 were able to complete the program. All the 40 participants (100.0%) who took the OSCEs were able to pass at the first attempt. Moreover, 94.9% of the trainees indicated that this program was able to cover the content necessary to use ultrasonography in home care settings. CONCLUSIONS: The results of this study suggest that the 7-day constipation POCUS educational program provided trainees with a foundational knowledge and skills to observe fecal retention in the colorectum. Thus, further educational program enhancements and clinical skill evaluations are needed to maximize the program's effectiveness in the future.

Vasohibin-1 expression in endothelium of tumor blood vessels regulates angiogenesis.

In this study, we characterized the significance of the vascular endothelial growth factor-inducible angiogenesis inhibitor vasohibin-1 to tumors. In pathological sections of non-small cell lung carcinoma, vasohibin-1 was present in the endothelial cells of blood vessels of the tumor stroma, but not in the lymphatics. In cancer cells, the presence of vasohibin-1 was associated with hypoxia-inducible factor 1alpha/vascular endothelial growth factor and fibroblast growth factor-2 expression. We then examined the function of vasohibin-1 in the mouse by subcutaneously inoculating with Lewis lung carcinoma cells. Resultant tumors in vasohibin-1(-/-) mice contained more immature blood vessels and fewer apoptotic tumor cells than tumors in wild-type mice. In wild-type mice that had been inoculated with Lewis lung carcinoma cells, tail vein injection of adenovirus containing the human vasohibin-1 gene inhibited tumor growth and tumor angiogenesis. Moreover, the remaining tumor vessels in adenoviral human vasohibin-1 gene-treated mice were small, round, and mature, surrounded by mural cells. The addition of adenoviral human vasohibin-1 gene to cisplatin treatment improved cisplatin's antitumor activity in mice. These results suggest that endogenous vasohibin-1 is not only involved in tumor angiogenesis, but when sufficient exogenous vasohibin-1 is supplied, it blocks sprouting angiogenesis by tumors, matures the remaining vessels, and enhances the antitumor effect of conventional chemotherapy.

[Alteration in antibody-mediated immunity in patients with rituximab-combined chemotherapy and incidence of herpes zoster].

Rituximab, a chimeric monoclonal antibody against the CD20 protein, has an antineoplastic effect resulting from antibody dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). In patients with rituximab-combined chemotherapy, a decline in immunoglobulin can be observed. This is more likely to cause virus reactivation, such as Herpes (H) zoster. However, this fact has not reported in a large-scale study. In order to research immunodeficiency conditions in patients with rituximab-combined therapy, we examined the alteration in immunoglobulin level throughout the treatment among 205 cases with B-cell lymphoma. We also studied the prevalence of H. zoster in those cases. The IgG level throughout the treatment was measured in 89 patients in the research. The median post-chemotherapy IgG level was 41.1% lower than its pre-chemotherapy IgG level. In 58 cases, the IgG level following chemotherapy was below the normal level. In 22 cases, the IgG level dropped to less than half of the pre-chemotherapy level. H. zoster developed in 17 cases (8.3%). There was no significant difference in IgG level between H. zoster-onset cases and non-H. zoster-onset cases. Antibody-mediated immunity can decrease greatly and prolong in cases with rituximab in combination with chemotherapy. Therefore, infection control is considered to be important.

Deep learning-based classification of rectal fecal retention and analysis of fecal properties using ultrasound images in older adult patients.

AIM: The present study aimed to analyze the use of machine learning in ultrasound (US)-based fecal retention assessment. METHODS: The accuracy of deep learning techniques and conventional US methods for the evaluation of fecal properties was compared. The presence or absence of rectal feces was analyzed in 42 patients. Eleven patients without rectal fecal retention on US images were excluded from the analysis; thus, fecal properties were analyzed in 31 patients. Deep learning was used to classify the transverse US images into three types: absence of feces, hyperechoic area, and strong hyperechoic area in the rectum. RESULTS: Of the 42 patients, 31 tested positive for the presence of rectal feces, zero were false positive, zero were false negative, and 11 were negative, indicating a sensitivity of 100% and a specificity of 100% for the detection of rectal feces in the rectum. Of the 31 positive patients, 14 had hard stools and 17 had other types. Hard stool was detected by US findings in 100% of the patients (14/14), whereas deep learning-based classification detected hard stool in 85.7% of the patients (12/14). Other stool types were detected by US findings in 88.2% of the patients (15/17), while deep learning-based classification also detected other stool types in 88.2% of the patients (15/17). CONCLUSIONS: The results showed that US findings and deep learning-based classification can detect rectal fecal retention in older adult patients and distinguish between the types of fecal retention.

Effectiveness of home care for fever treatment in older people: A case-control study compared with hospitalized care.

AIM: To examine whether the outcomes of fever treatment through home care differ from those through hospitalized care for older people who regularly receive home care in Japan. METHODS: A retrospective survey of medical record-based data for 679 older people who regularly received home care provided by a clinic in Japan. From these data, 61 fever cases (21 cases treated in the hospital and 40 treated at home and assigned to the hospitalized and home-care groups, respectively) were selected for analysis through a matching process. We compared the two groups in terms of mortality rate at 90 days after fever onset, and concerning changes in respective ranks for "Degree of Independent Living for the Elderly with Disability" and "Degree of Independent Living for the Elderly with Dementia" from immediately before fever onset to 90 days after fever onset. RESULTS: The mortality rate tended to be higher in the hospitalized group than in the home-care group (33% vs. 13%, respectively, P = 0.05). The hospitalized group also had a higher proportion of patients whose disability had worsened (43% vs. 23%, respectively, P = 0.16) and a significantly higher proportion of patients whose dementia had worsened (29% vs. 6%, respectively, P = 0.03). CONCLUSIONS: Our findings suggest that home care is more effective than hospitalized care for treating fever in older people who regularly receive home care in Japan, as it leads to lower mortality and better maintenance of activities of daily living capabilities. Geriatr Gerontol Int 2020; 20: 482-487.

Safety and efficacy of a defecation care algorithm based on ultrasonographic bowel observation in Japanese home-care settings: a single-case, multiple-baseline study.

AIM: To verify the efficacy of defecation care based on handheld ultrasonographic observations for functional constipation by visiting nurses skilled in bowel ultrasonography. METHODS: Home-care patients with suspected functional constipation receiving nursing visits were recruited in this multiple-baseline, single-case experiment with intervention points shifted by 1 week. A total of 15 older adults were categorized into 3-, 4-, 5- or 6-week intervention phases. Ultrasonographic observations of fecal retention in the colorectum and defecation care based on observations during the ordinal physical assessment were reviewed. Tau-U was used for confirming the efficacy of the intervention by measuring the number of non-artificial and artificial defecations, as well as hard stools per week, and the amount of non-stimulant and stimulant laxatives, enemas and suppositories per week. For evaluating safety, adverse events, such as bowel obstruction and incontinence-associated dermatitis, were confirmed. RESULTS: No adverse events were observed. Statistical analysis showed that hard stools and artificial defecation reduced, and that their effect sizes were significant (Tau = -0.48, P < 0.01; Tau = -0.53, P < 0.01). Even the amounts of stimulant laxative and glycerin enema reduced, and their effect sizes were significant (Tau = -0.56, P < 0.01; Tau = -0.34, P = 0.04). CONCLUSIONS: Thus, defecation care based on ultrasonographic assessment by nurses in home-care settings is safe and effective for improving constipation symptoms and reducing laxative use. Geriatr Gerontol Int 2020; ••: ••-••.