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Cortical deafness as a sole manifestation of ischemic cerebrovascular disease
Abstracts / Journal of the Neurological Sciences 333 (2013) e215–e278
Conclusion: Acute aSAH strongly influences the composition of leukocytes in the peripheral blood. In particular, we found a decrease of nonclassical monocyte count concomitantly with decreased numbers of CD3+, CD4+ and iNKT cells. doi:10.1016/j.jns.2013.07.916
Abstract — WCN 2013 No: 2225 Topic: 3 — Stroke Is thrombolysis realizable at the Department of Neurology, Fann Teaching Hospital, Dakar-Senegal? D. Coulibaly, Y. Bassong, P. Mbonda, K. Touré, A.G. Diop, M.M. Ndiaye. Neurology, Cheikh Anta Diop, Dakar, Senegal Background and purpose: Stroke is a real health problem with a high morbidity and mortality in developing countries. This figure is increasing and worsening because of a problem of management. Nevertheless, the organization of care in the acute phase significantly reduces the cost, morbidity and mortality of stroke. Among these treatments, thrombolysis is the most effective therapeutic means to prevent lasting disability. However neurological clinics exist in Africa, thrombolysis in stroke patients is not updated. The study focused on the feasibility of thrombolysis in our neurological department. Methods: This is a prospective study from September 2010 to April 2012 in a population of patients attending the Department of Neurology, Fann Teaching Hospital of Dakar-Senegal for stroke. Data on sociodemographic, lifestyle, delay to attend the clinic and to realize the CT scan of the brain were collected. We performed univariate and multivariate comparing the time of consultation and achievements of brain scan with socioeconomic data. Results: Data of 285 patients was collected. They had a mean age of 56.5 years, male (50%), and ischemic stroke (73%). The main risk factors for stroke were: hypertension and diabetes. The consultation period was within 3 h for 19.8% and within 6 h for 15.1%. 23.3% came by ambulance and 66.7% by public transport. 9% had the CT scan performed within 3 h and 18% within 6 h. No statistically significant difference between time compared to variables of interest before 6 h was observed. Conclusions: Thrombolysis appears feasible in our clinic. doi:10.1016/j.jns.2013.07.917
Abstract — WCN 2013 No: 2278 Topic: 3 — Stroke Time is brain: Stroke thrombolysis in Brunei Darussalam G.C. Chana, U. Meyding-Lamadea,b. aDepartment of Neurology, Neuroscience Stroke and Rehabilitation Centre, Bandar Seri Begawan, Brunei; bDepartment of Neurology, Krankenhaus Nordwest, Frankfurt/Main, Germany Background: Stroke is emerging as a major public health problem for Brunei Darussalam. The Neuroscience, Stroke and Rehabilitation Centre (NSRC) has established a dedicated stroke unit since 2010. Objective: To assess the demographic of patients admitted with ischaemic stroke into NSRC who were within the 4.5 hours thrombolytic window. Methods: Medical case-notes of all patients admitted with stroke (ischemic or haemorrhagic) from July 2010 to October 2012 were reviewed. Data collected included age, gender, referral centres, time of symptoms, time of arrival in NSRC, time of thrombolysis and length of stay.
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Results: Out of 456 charts reviewed, 21 patients (5%) received intravenous thrombolysis with Alteplase. There were 13 (62%) males and 8 (38%) females. 86% of patients were referred from Brunei Darussalam main hospital (RIPAS) while 14% were referred from Jerudong Park Medical Centre. The mean age of patients was 56 ± 12 years (range 23–88). The mean time from onset of symptoms to iv needle thrombolysis was 179 ± 62 min. The mean door to iv needle thrombolysis was 48 ± 22 min. Thus the mean time from onset of symptoms to reaching our unit (door) was 131 min. Conclusion: In our preliminary study (with small number of patients), there is a quick and efficient door to needle thrombolysis time of 48 min. However there is a need to improve the time delay (131 min) from the onset of symptoms to reaching our stroke unit. doi:10.1016/j.jns.2013.07.918
Abstract — WCN 2013 No: 2153 Topic: 3 — Stroke Demographic of stroke: A comparative study between Brunei Darussalam Neuroscience, Stroke and Rehabilitation Centre and Krankenhaus Nordwest, Frankfurt, Germany G.C. Chana, B. Bassab, U. Meyding-Lamadea,c. aDepartment of Neurology, Neuroscience Stroke and Rehabilitation Centre, Bandar Seri Begawan, Brunei; bDepartment of Neurology, Frankfurt/Main, Germany; cKrankenhaus Nordwest, Frankfurt/Main, Germany Background: The Neuroscience, Stroke and Rehabilitation Centre (NSRC) of Brunei Darussalam has been working in collaboration with Krankenhaus Nordwest Hospital, Frankfurt since 2010. Objective: To compare the demographic of patients between the two centres. Methods: All patients admitted with stroke (ischemic or haemorrhagic) from July 2010 to November 2011 to both centres were reviewed. Data collected included age and gender. Results: In the Brunei data, 254 patients (59% male, 41% female) were studied (mean age of 60 ± 14 years, range 22–95). The male to female ratio in age group 21–30 is 1:0, age group 31–40 is 3:1, age group 41–50 is 2:1, age group 51–60 is 3:2, age group 61–70 is 1:1, age group 71–80 is 1:1, and age group N 80 is 1:1. In the Frankfurt Krankenhaus Nordwest data, 3498 patients (50% male, 50% female) were studied (mean age 72.45 ± 20 years, range 19–103). The male to female ratio in age group 21–30 is 1:3, age group 31–40 is 1:2, age group 41–50 is 1:1, age group 51–60 is 2:1, age group 61–70 is 2:1, age group 71–80 is 1:1, and age group N 80 is 1:2. Conclusion: Comparing Brunei NSRC to Frankfurt Krankenhaus Nordwest the mean age of stroke disease is 12 years younger in the Brunei patients and higher male to female ratio in the age group of 31–40 and 41–50. This warrants further study to identify the possible reasons for the demographic difference between an Asian and Western population. doi:10.1016/j.jns.2013.07.919
Abstract — WCN 2013 No: 2200 Topic: 3 — Stroke Cortical deafness as a sole manifestation of ischemic cerebrovascular disease E. Papageorgiou, G. Matikas, X. Papastergios, V. Koukouni, G. Gekas. Neurology Department General Hospital of Nikaia, Athens, Greece
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Abstracts / Journal of the Neurological Sciences 333 (2013) e215–e278
Background: Cortical deafness is a very rare condition characterized by the complete disruption of central auditory processing with intact peripheral auditory function. Objective: To describe a case of cortical deafness associated with ischemic cerebrovascular disease. Patients and methods: A 61 year-old female with a history of arterial hypertension presented to our department complaining of a sudden complete hearing loss. On examination, she was alert but slightly confused and agitated. Her spontaneous speech was fluent with occasional paraphasic errors. She was unable to follow verbal commands, but could understand simple written information. She appeared totally deaf, with no startle response to loud sounds. The rest of the neurological examination was unremarkable. Brain CT scan demonstrated a chronic right temporoparietal ischemic infarct. Otologic examination revealed no evidence of external or middle ear disease. Audiometry showed normal middle ear reflexes. Brainstem auditory evoked potentials were normal, consistent with normal auditory processing up to and including the inferior colliculi. An MRI scan demonstrated the old right temporoparietal infarct and an additional hyperacute ischemic infarct in the left posterior parietal area, extending into the Heschl's gyrus, the superior temporal gyrus and the Sylvian fissure. In three months' follow-up, the patient showed no improvement and she was able to communicate only through reading and writing. Conclusion: Our case emphasizes on cortical deafness as a rare sole manifestation of ischemic cerebrovascular disease associated with bilateral damage of the primary auditory cortex. doi:10.1016/j.jns.2013.07.920
Abstract — WCN 2013 No: 1900 Topic: 3 — Stroke Central obesity in the poorest region in Chile R.J. Rivasa,b, C.A. Klappb,c, C.A. Darochb,d, H.M. Vásquezb,d. a Neurology Department, Universidad de La Frontera, Chile; bStroke Unit, Clínica Alemana de Temuco, Temuco, Chile; cNeurology Department, Clínica Alemana de Temuco, Temuco, Chile; dNutrition Department, Clínica Alemana de Temuco, Temuco, Chile Background: Stroke is the first most common specific cause of death in Chile, since 2008. The increased risk in our region is explained by the prevalence of poverty, diabetes, a sedentary lifestyle and overweight. Object: Is to assess the waist circumference (WC) in Clínica Alemana Temuco, during January 2011 to March 2013, in patients with a stroke. Methods: We evaluated patients with a stroke diagnosis, in our primary Stroke Unit, who were hospitalized for ≥72 h. Waist circumference (WC) was measured according to WHO's recommendations, by two nutritionists. The study patients were divided into 3 groups according to WC for cardiovascular risk, low risk (LR): b94 cm (men); b80 cm (women); moderate risk (MR): 94–102 cm (men); 80–88 cm (women); and high risk (HR): N102 cm (men); N88 cm (women). We obtained a diagnosis of central obesity (CO) using NCEP-ATP-III criteria. Results: 81 patients were included. 48 were males (59.3%). Men mean aged: 62 years (32–89), mean WC: 103.9 (SD: ±9.9). BMI: 29. LR: 14.6%, MR: 37.5%, HR: 47.9% (CO). Women mean age: 57.4 years (35–81). Mean WC: 102.3 (SD: ±13.6), BMI: 29.9. LR: 3%; MR: 15.2%; HR: 81.8% (CO). Total sample corresponds to LR: 9.9%, MR: 28.4%; and HR: 61.7% (CO). Conclusion: Central obesity is a major risk factor for cardiovascular disease. This series of cases only shows that the problem is very important in Chile. The obesity and central obesity are epidemic. We
should perform behaviors to lower these indicators, with much education and government guidelines. doi:10.1016/j.jns.2013.07.921
Abstract — WCN 2013 No: 2198 Topic: 3 — Stroke Preliminary evaluation of diffusion kurtosis imaging in acute stroke patients Y.-L. Guoa, S.-J. Lia, P. Zhe Sunb, R.-H. Wua. aDepartment of Radiology, The Second Affiliated Hospital, Shantou University Medical College, Shantou, China; bAthinoula A. Martinos Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Aims: To translate and evaluate diffusion kurtosis imaging (DKI) in stroke patients. Methods: Four patients underwent DKI and conventional MRI (including T1WI, T2WI, FLAIR and DWI) using a GE 1.5T HDx echo speed plus an MRI scanner. Mean kurtosis (MK), radial kurtosis (Kr) and axial kurtosis (Ka) were derived using DKI software in GE ADW4.3 workstation. Fourteen regions of interest (ROI) were outlined in infarction regions of stroke patients, including 2 ROIs in super-acute, 3 ROIs in acute, 6 ROIs in subacute and 3 ROIs in chronic lesions. The stroke duration was determined from onset time and DWI signal intensity. Stroke prognosis was evaluated by follow-up MRI and clinical manifestations. Results: During super-acute stroke, regions of hyperintensive MK and Kr progressed to infarction with mild bleeding without noticeable DWI and ADC abnormalities. For the case of sub-acute stroke, DKI (MK and Kr) appeared hypointensive without significant change in DWI and ADC maps. In addition, 10 ROIs showed abnormality in both DKI and DWI/ADC maps. Conclusions: DKI displayed contrast different from the standard DWI and ADC maps. DKI remains promising to address false negative signals in the standard DWI and ADC maps, and complement existing stroke MRI for improved stroke diagnosis. doi:10.1016/j.jns.2013.07.922
Abstract — WCN 2013 No: 2301 Topic: 3 — Stroke Predictors of pneumonia in acute stroke inpatients in emergency unit S.R. Almeidaa, M. Bahiab, F.O. Limab, T.A.M.O. Cardosoa, I. Paschoalc, L.M. Lia, Neurovascular Disease. a Neurology, University of Campinas, UNICAMP, Campinas, Brazil; b Medical Pathophysiology Department, University of Campinas, UNICAMP, Campinas, Brazil; cMedical Clinic, University of Campinas, UNICAMP, Campinas, Brazil Background: Pneumonia is a serious complication in acute stroke patients. Several mechanisms might be implicated including impairment of the immune system and aspiration. The analyses of clinical predictors are useful to guide the clinical management and to adopt preventive measures in order to improve the patients' outcome. Objective: To determine the independent predictors of pneumonia in patients with acute stroke. Methods: This is a retrospective study from July to December 2011. All patients admitted with a diagnosis of stroke in an academic medical center were included. We review all the medical charts and
Conclusion: Acute aSAH strongly influences the composition of leukocytes in the peripheral blood. In particular, we found a decrease of nonclassical monocyte count concomitantly with decreased numbers of CD3+, CD4+ and iNKT cells. doi:10.1016/j.jns.2013.07.916
Abstract — WCN 2013 No: 2225 Topic: 3 — Stroke Is thrombolysis realizable at the Department of Neurology, Fann Teaching Hospital, Dakar-Senegal? D. Coulibaly, Y. Bassong, P. Mbonda, K. Touré, A.G. Diop, M.M. Ndiaye. Neurology, Cheikh Anta Diop, Dakar, Senegal Background and purpose: Stroke is a real health problem with a high morbidity and mortality in developing countries. This figure is increasing and worsening because of a problem of management. Nevertheless, the organization of care in the acute phase significantly reduces the cost, morbidity and mortality of stroke. Among these treatments, thrombolysis is the most effective therapeutic means to prevent lasting disability. However neurological clinics exist in Africa, thrombolysis in stroke patients is not updated. The study focused on the feasibility of thrombolysis in our neurological department. Methods: This is a prospective study from September 2010 to April 2012 in a population of patients attending the Department of Neurology, Fann Teaching Hospital of Dakar-Senegal for stroke. Data on sociodemographic, lifestyle, delay to attend the clinic and to realize the CT scan of the brain were collected. We performed univariate and multivariate comparing the time of consultation and achievements of brain scan with socioeconomic data. Results: Data of 285 patients was collected. They had a mean age of 56.5 years, male (50%), and ischemic stroke (73%). The main risk factors for stroke were: hypertension and diabetes. The consultation period was within 3 h for 19.8% and within 6 h for 15.1%. 23.3% came by ambulance and 66.7% by public transport. 9% had the CT scan performed within 3 h and 18% within 6 h. No statistically significant difference between time compared to variables of interest before 6 h was observed. Conclusions: Thrombolysis appears feasible in our clinic. doi:10.1016/j.jns.2013.07.917
Abstract — WCN 2013 No: 2278 Topic: 3 — Stroke Time is brain: Stroke thrombolysis in Brunei Darussalam G.C. Chana, U. Meyding-Lamadea,b. aDepartment of Neurology, Neuroscience Stroke and Rehabilitation Centre, Bandar Seri Begawan, Brunei; bDepartment of Neurology, Krankenhaus Nordwest, Frankfurt/Main, Germany Background: Stroke is emerging as a major public health problem for Brunei Darussalam. The Neuroscience, Stroke and Rehabilitation Centre (NSRC) has established a dedicated stroke unit since 2010. Objective: To assess the demographic of patients admitted with ischaemic stroke into NSRC who were within the 4.5 hours thrombolytic window. Methods: Medical case-notes of all patients admitted with stroke (ischemic or haemorrhagic) from July 2010 to October 2012 were reviewed. Data collected included age, gender, referral centres, time of symptoms, time of arrival in NSRC, time of thrombolysis and length of stay.
e235
Results: Out of 456 charts reviewed, 21 patients (5%) received intravenous thrombolysis with Alteplase. There were 13 (62%) males and 8 (38%) females. 86% of patients were referred from Brunei Darussalam main hospital (RIPAS) while 14% were referred from Jerudong Park Medical Centre. The mean age of patients was 56 ± 12 years (range 23–88). The mean time from onset of symptoms to iv needle thrombolysis was 179 ± 62 min. The mean door to iv needle thrombolysis was 48 ± 22 min. Thus the mean time from onset of symptoms to reaching our unit (door) was 131 min. Conclusion: In our preliminary study (with small number of patients), there is a quick and efficient door to needle thrombolysis time of 48 min. However there is a need to improve the time delay (131 min) from the onset of symptoms to reaching our stroke unit. doi:10.1016/j.jns.2013.07.918
Abstract — WCN 2013 No: 2153 Topic: 3 — Stroke Demographic of stroke: A comparative study between Brunei Darussalam Neuroscience, Stroke and Rehabilitation Centre and Krankenhaus Nordwest, Frankfurt, Germany G.C. Chana, B. Bassab, U. Meyding-Lamadea,c. aDepartment of Neurology, Neuroscience Stroke and Rehabilitation Centre, Bandar Seri Begawan, Brunei; bDepartment of Neurology, Frankfurt/Main, Germany; cKrankenhaus Nordwest, Frankfurt/Main, Germany Background: The Neuroscience, Stroke and Rehabilitation Centre (NSRC) of Brunei Darussalam has been working in collaboration with Krankenhaus Nordwest Hospital, Frankfurt since 2010. Objective: To compare the demographic of patients between the two centres. Methods: All patients admitted with stroke (ischemic or haemorrhagic) from July 2010 to November 2011 to both centres were reviewed. Data collected included age and gender. Results: In the Brunei data, 254 patients (59% male, 41% female) were studied (mean age of 60 ± 14 years, range 22–95). The male to female ratio in age group 21–30 is 1:0, age group 31–40 is 3:1, age group 41–50 is 2:1, age group 51–60 is 3:2, age group 61–70 is 1:1, age group 71–80 is 1:1, and age group N 80 is 1:1. In the Frankfurt Krankenhaus Nordwest data, 3498 patients (50% male, 50% female) were studied (mean age 72.45 ± 20 years, range 19–103). The male to female ratio in age group 21–30 is 1:3, age group 31–40 is 1:2, age group 41–50 is 1:1, age group 51–60 is 2:1, age group 61–70 is 2:1, age group 71–80 is 1:1, and age group N 80 is 1:2. Conclusion: Comparing Brunei NSRC to Frankfurt Krankenhaus Nordwest the mean age of stroke disease is 12 years younger in the Brunei patients and higher male to female ratio in the age group of 31–40 and 41–50. This warrants further study to identify the possible reasons for the demographic difference between an Asian and Western population. doi:10.1016/j.jns.2013.07.919
Abstract — WCN 2013 No: 2200 Topic: 3 — Stroke Cortical deafness as a sole manifestation of ischemic cerebrovascular disease E. Papageorgiou, G. Matikas, X. Papastergios, V. Koukouni, G. Gekas. Neurology Department General Hospital of Nikaia, Athens, Greece
e236
Abstracts / Journal of the Neurological Sciences 333 (2013) e215–e278
Background: Cortical deafness is a very rare condition characterized by the complete disruption of central auditory processing with intact peripheral auditory function. Objective: To describe a case of cortical deafness associated with ischemic cerebrovascular disease. Patients and methods: A 61 year-old female with a history of arterial hypertension presented to our department complaining of a sudden complete hearing loss. On examination, she was alert but slightly confused and agitated. Her spontaneous speech was fluent with occasional paraphasic errors. She was unable to follow verbal commands, but could understand simple written information. She appeared totally deaf, with no startle response to loud sounds. The rest of the neurological examination was unremarkable. Brain CT scan demonstrated a chronic right temporoparietal ischemic infarct. Otologic examination revealed no evidence of external or middle ear disease. Audiometry showed normal middle ear reflexes. Brainstem auditory evoked potentials were normal, consistent with normal auditory processing up to and including the inferior colliculi. An MRI scan demonstrated the old right temporoparietal infarct and an additional hyperacute ischemic infarct in the left posterior parietal area, extending into the Heschl's gyrus, the superior temporal gyrus and the Sylvian fissure. In three months' follow-up, the patient showed no improvement and she was able to communicate only through reading and writing. Conclusion: Our case emphasizes on cortical deafness as a rare sole manifestation of ischemic cerebrovascular disease associated with bilateral damage of the primary auditory cortex. doi:10.1016/j.jns.2013.07.920
Abstract — WCN 2013 No: 1900 Topic: 3 — Stroke Central obesity in the poorest region in Chile R.J. Rivasa,b, C.A. Klappb,c, C.A. Darochb,d, H.M. Vásquezb,d. a Neurology Department, Universidad de La Frontera, Chile; bStroke Unit, Clínica Alemana de Temuco, Temuco, Chile; cNeurology Department, Clínica Alemana de Temuco, Temuco, Chile; dNutrition Department, Clínica Alemana de Temuco, Temuco, Chile Background: Stroke is the first most common specific cause of death in Chile, since 2008. The increased risk in our region is explained by the prevalence of poverty, diabetes, a sedentary lifestyle and overweight. Object: Is to assess the waist circumference (WC) in Clínica Alemana Temuco, during January 2011 to March 2013, in patients with a stroke. Methods: We evaluated patients with a stroke diagnosis, in our primary Stroke Unit, who were hospitalized for ≥72 h. Waist circumference (WC) was measured according to WHO's recommendations, by two nutritionists. The study patients were divided into 3 groups according to WC for cardiovascular risk, low risk (LR): b94 cm (men); b80 cm (women); moderate risk (MR): 94–102 cm (men); 80–88 cm (women); and high risk (HR): N102 cm (men); N88 cm (women). We obtained a diagnosis of central obesity (CO) using NCEP-ATP-III criteria. Results: 81 patients were included. 48 were males (59.3%). Men mean aged: 62 years (32–89), mean WC: 103.9 (SD: ±9.9). BMI: 29. LR: 14.6%, MR: 37.5%, HR: 47.9% (CO). Women mean age: 57.4 years (35–81). Mean WC: 102.3 (SD: ±13.6), BMI: 29.9. LR: 3%; MR: 15.2%; HR: 81.8% (CO). Total sample corresponds to LR: 9.9%, MR: 28.4%; and HR: 61.7% (CO). Conclusion: Central obesity is a major risk factor for cardiovascular disease. This series of cases only shows that the problem is very important in Chile. The obesity and central obesity are epidemic. We
should perform behaviors to lower these indicators, with much education and government guidelines. doi:10.1016/j.jns.2013.07.921
Abstract — WCN 2013 No: 2198 Topic: 3 — Stroke Preliminary evaluation of diffusion kurtosis imaging in acute stroke patients Y.-L. Guoa, S.-J. Lia, P. Zhe Sunb, R.-H. Wua. aDepartment of Radiology, The Second Affiliated Hospital, Shantou University Medical College, Shantou, China; bAthinoula A. Martinos Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Aims: To translate and evaluate diffusion kurtosis imaging (DKI) in stroke patients. Methods: Four patients underwent DKI and conventional MRI (including T1WI, T2WI, FLAIR and DWI) using a GE 1.5T HDx echo speed plus an MRI scanner. Mean kurtosis (MK), radial kurtosis (Kr) and axial kurtosis (Ka) were derived using DKI software in GE ADW4.3 workstation. Fourteen regions of interest (ROI) were outlined in infarction regions of stroke patients, including 2 ROIs in super-acute, 3 ROIs in acute, 6 ROIs in subacute and 3 ROIs in chronic lesions. The stroke duration was determined from onset time and DWI signal intensity. Stroke prognosis was evaluated by follow-up MRI and clinical manifestations. Results: During super-acute stroke, regions of hyperintensive MK and Kr progressed to infarction with mild bleeding without noticeable DWI and ADC abnormalities. For the case of sub-acute stroke, DKI (MK and Kr) appeared hypointensive without significant change in DWI and ADC maps. In addition, 10 ROIs showed abnormality in both DKI and DWI/ADC maps. Conclusions: DKI displayed contrast different from the standard DWI and ADC maps. DKI remains promising to address false negative signals in the standard DWI and ADC maps, and complement existing stroke MRI for improved stroke diagnosis. doi:10.1016/j.jns.2013.07.922
Abstract — WCN 2013 No: 2301 Topic: 3 — Stroke Predictors of pneumonia in acute stroke inpatients in emergency unit S.R. Almeidaa, M. Bahiab, F.O. Limab, T.A.M.O. Cardosoa, I. Paschoalc, L.M. Lia, Neurovascular Disease. a Neurology, University of Campinas, UNICAMP, Campinas, Brazil; b Medical Pathophysiology Department, University of Campinas, UNICAMP, Campinas, Brazil; cMedical Clinic, University of Campinas, UNICAMP, Campinas, Brazil Background: Pneumonia is a serious complication in acute stroke patients. Several mechanisms might be implicated including impairment of the immune system and aspiration. The analyses of clinical predictors are useful to guide the clinical management and to adopt preventive measures in order to improve the patients' outcome. Objective: To determine the independent predictors of pneumonia in patients with acute stroke. Methods: This is a retrospective study from July to December 2011. All patients admitted with a diagnosis of stroke in an academic medical center were included. We review all the medical charts and