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Biomedical subjects

F A Gries

Publications and source records attributed to F A Gries.

At least 55 records · Page 3Linked to original sources

[Optic neuropathy in type-1 diabetes and acetylsalicylic acid-refractory thrombocyte activation].

A 26-year-old female with severe complications from type I diabetes mellitus of 17 years' duration (proliferative retinopathy, nephropathy with renal failure and nephrotic syndrome) developed rapid deterioration of vision in the right eye to 6/60 over a period of several weeks. There were no other neurological signs. Ophthalmological examination showed no worsening of the diabetic retinopathy, but the presence of bilateral optic atrophy, confirmed by visual evoked potentials. CT scan did not reveal any retrobulbar process, and MR scans of both the optic nerves and the visual pathways were unremarkable. The clinical features and the investigations pointed towards ischaemic optic atrophy. Detailed platelet studies showed intravascular platelet activation and an ADP-inducible increase in aggregation, although thromboxane formation was almost absent because of cyclooxygenase inhibition by acetylsalicylic acid. These findings suggest that the ischaemia was due to microcirculatory disturbances secondary to diabetic microangiopathy and platelet hyperreactivity.

Adult↗

Platelets in diabetes: the role in the hemostatic regulation in atherosclerosis.

Vascular diseases and related complications still represent the main cause of death in diabetic patients. Neuropathy, nephropathy, retinopathy, and disturbed nutritive tissue perfusion may result from reduced capillary microcirculation. These disturbances are diabetes specific. Macroangiopathy does not differ structurally from atherosclerotic lesions of nondiabetic subjects, but leads to accelerated cerebral, coronary, and peripheral artery disease. Occurrence of life-terminating thrombotic events, which are superimposed on those vascular lesions, are increased. Thus, morbidity and mortality of diabetics depend mainly on vascular complications. Normal blood flow is a prerequisite of adequate organ perfusion and results from vasomotion, plasma components, corpuscular blood elements, vascular architecture, and the undisturbed interaction of these components at the endothelial interface. Functional thromboresistance of the endothelial layer is reduced in the diabetic state. Increased intravascular thrombin generation, reduced fibrinolytic potential, and hyperactive platelets lead to a prethrombotic state. This thrombotic diathesis increases the permanent danger of acute flow interruption. Activated platelets operate by three mechanisms: (1) Microembolization of the capillaries; (2) local progression of preexisting vascular lesions by secretion of constrictive, mitogenic, and oxidative substances; (3) trigger of the prognosis-limiting arterial thrombotic event. We were able to show that the increased functional properties of diabetic platelets result from the primary release of larger platelets with enhanced thromboxane formation capacity and increased numbers of functional glycoprotein receptors GPIb and GPIIb/IIIa, which are synthesized in the megakaryocytes. The megakaryocyte-platelet system is turned on in diabetes mellitus. It could be demonstrated with the Duesseldorf III method of flow cytometric activation marker testing (CD62, CD63, thrombospondin) that predominantly large platelets circulate in an activated state in diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗

Mortality in diabetic patients with cardiovascular autonomic neuropathy.

Cardiovascular autonomic diabetic neuropathy (CADN) may carry an increased risk of mortality. However, in previous studies the prognosis of patients with CADN seemed to be influenced by life-threatening macro- and microvascular complications which had already been present at the start of the study period. Between 1981 and 1983, 1015 diabetic patients have been examined for CADN (abnormal heart rate variation at rest and during deep respiration) at the Diabetes Research Institute, Düsseldorf. Thirty-five patients (28 with Type 1 diabetes, 7 with Type 2 diabetes) with CADN have been retrospectively recruited and reviewed 8 years later and compared with 35 patients without CADN who were matched for sex, age, and duration of diabetes. Exclusion criteria for entry into the study included severe micro- or macrovascular complications, such as proliferative retinopathy, proteinuria or symptomatic coronary artery disease. During the 8-year observation period, 8 patients with CADN and 1 patient without CADN died. The survival rate estimates steadily declined in patients with CADN over the whole period studied. The 8-year survival rate estimate in patients with CADN was 77% compared with 97% in those with normal autonomic function (p < 0.05). Deaths were mainly due to macrovascular diseases (n = 3) and sudden unexpected deaths (n = 3). One patient with CADN died after an episode of severe hypoglycaemia. Among the decreased patients, coefficient of variation of R-R intervals during deep breathing was significantly reduced when compared with those who survived (1.04 +/- 0.5% vs 1.87 +/- 1.0%; p < 0.05), and symptoms of autonomic neuropathy (orthostatic hypotension, gastroparesis, gustatory sweating) were more frequent (7/8 vs 10/27 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Tibial nerve somatosensory evoked potentials at various stages of peripheral neuropathy in insulin dependent diabetic patients.

To determine whether central nervous conduction deficits are related to the degree of peripheral neuropathy somatosensory evoked potentials (SEP) were measured after tibial nerve stimulation in 51 healthy subjects aged 39.3 (SE 2.0, (range 21-71) years and 100 insulin dependent diabetic patients aged 37.3 (1.5, 18-73) years. Five criteria were used for staging of peripheral neuropathy: nerve conduction; thermal discrimination threshold; vibration perception threshold; tendon reflexes; and neuropathic symptoms. Thirty seven patients had fewer than two abnormalities among the first four criteria and no symptoms (stage 0 = no neuropathy), 37 had 2 or more abnormalities but no symptoms (stage 1 = subclinical neuropathy); 26 had 2 or more abnormalities in conjunction with symptoms (stage 2 = symptomatic neuropathy). Multiple regression analysis was used to define the age and height dependent limits of normal of SEP at the 97.5th and 2.5th centiles. In five patients with stage 1, seven patients with stage 2, but no patient with stage 0 the individual SEP components were unrecordable. The relative frequencies of abnormally prolonged or non-evokable popliteal N8 latency as well as cortical N33 latency and N33/P40 amplitude increased significantly from stage 0 (3-30%) to stage 1 (22-62%) and stage 2 (46-84%) (p < 0.05 for each component and stage). The numbers and percentages of abnormal recordable spinal N22-30 and supraspinal N30-33 interpeak latencies were two (6.3%) and four (11.8%) in patients with stage 0, but these rates did not increase in subjects with stage 1 or 2. The components of SEP were significantly associated with the indices of peripheral and autonomic function tests. There were no major relations between the latencies of SEP and duration of diabetes or prevailing glycaemic control. These findings suggest that the degree of dysfunction along the somatosensory afferent pathways in insulin dependent diabetic patients depends on the stage of peripheral neuropathy; is not related to the degree of glycaemic control or duration of diabetes; and can be characterized mainly by an alteration of the cortical sensory complex and peripheral transmission delay, while spinal and supraspinal conduction deficits are detected infrequently.

Adult↗

Platelet membrane activation markers are predictive for increased risk of acute ischemic events after PTCA.

BACKGROUND: We wished to investigate whether platelet activation is related to the clinical outcome during the 24 hours immediately after elective percutaneous transluminal coronary angioplasty (PTCA). METHODS AND RESULTS: In 102 patients with high-grade coronary stenosis admitted for elective PTCA, preprocedural platelet activation was characterized by flow cytometric measurement of the proteins CD62, CD63, and thrombospondin expressed on the platelet surface membrane. The prevalence of acute ischemic events during the 24 hours immediately after the procedure was then related to the pre-PTCA platelet activation status. Fifty-six patients were classified as "nonactivated," whereas 46 patients showed an increased percentage of activated platelets. Two patients developed acute occlusion (1.96%) and four patients high-grade restenosis (3.92%), as confirmed by second-look coronary angiography. All events occurred in patients classified as "activated" (six of 46, or 13%). None of these patients received beta-blocker medication, which was associated with lower expression of platelet membrane activation markers. In the nonactivated patient group, no clinical events were found (0 of 56, or 0%). This difference in prevalence is significant (p = 0.007). CONCLUSIONS: We conclude that analysis of platelet membrane activation markers may help to predict an increased risk of acute ischemic events after angioplasty.

Angioplasty, Balloon, Coronary↗

Prevalence and clinical correlates of cardiovascular autonomic and peripheral diabetic neuropathy in patients attending diabetes centers. The Diacan Multicenter Study Group.

The objective of the study was to evaluate the prevalence of and the factors associated with cardiovascular autonomic diabetic neuropathy (CADN) and peripheral neuropathy in patients attending clinical and outpatient diabetes centers. The design was a multicenter cross section study with random selection of patients with Type 1 or Type 2 diabetes from seventeen German, three Swiss, and two Austrian inpatient and outpatient diabetes centers. A total of 1,642 patients were recruited, 1,171 of whom (Type 1: n = 647, age: 11-69 years; Type 2: n = 524, age: 16-72 years) were studied. Measurements and results. The following six autonomic function tests based on heart rate variation were used for the diagnosis of CADN: coefficient of variation and power spectrum in the low- and mid-frequency bands at rest, mean circular resultant during deep breathing, Valsalva ratio, and max/min 30:15 ratio to standing. The age-dependent lower limit of the normal range in these tests had previously been defined at the 2.3 centile in 120 healthy subjects. Definite CADN defined by the strict criterion of abnormal results in > or = 3 of these 6 tests was detected in 16.8% of the Type 1 and 22.1% of the Type 2 diabetic patients (p < 0.05). The corresponding rates of borderline CADN defined as the presence of 2 abnormalities were 8.5% and 12.2%, respectively (p < 0.05). Peripheral neuropathy defined as the presence of > or = 2 abnormalities among 3 criteria (neuropathic symptoms, absent tendon reflexes, and abnormal malleolar vibration perception threshold) was observed in 17.1% of Type 1 and 34.8% of Type 2 diabetic patients (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Association of elevated serum uric acid with coronary heart disease in diabetes mellitus.

The relationship between elevated serum uric acid (SUA) and coronary heart disease (CHD) is discussed controversially. In this cross-sectional study, we evaluated the association between hyperuricaemia and small- and large-vessel diseases in diabetic patients by analyzing clinical data of 7847 diabetic patients of both sexes (Type 1 diabetes: n = 3800, Type 2 diabetes: n = 4047). Elevated serum uric acid was defined as concentrations > 7.0 mg/dl in men and > 6.6 mg/dl in women. The prevalence of hyperuricaemia was dependent on age and duration of the disease in Type 1 diabetic patients, whereas in recently diagnosed Type 2 diabetic patients the prevalence of elevated uric acid levels was higher than in patients with long-standing Type 1 diabetes, without any further increase with longer duration of the disease. An elevated uric acid level was also associated with body weight, hypertension and nephropathy in both types of diabetes and in both sexes. In women, hyperuricaemia was correlated with the presence of coronary heart disease both in Type 1 and Type 2 diabetes (p < 0.05). The exclusion of hypertension and nephropathy in the multiple logistic regression had no effect on these associations. However, after adjustment for these two factors a significant correlation between hyperuricaemia and coronary heart disease was also found in Type 2 diabetic men. In addition, increased serum uric acid was associated with gangrene in male Type 2 diabetic patients (p < 0.05). These results suggest that elevated uric acid levels are correlated with the presence of coronary heart disease in female rather than in male diabetic patients, independently of hypertension and nephropathy.

Adolescent↗

The pharmacokinetics of two different concentrations of short-acting insulin, intermediate-acting insulin, and an insulin mixture following subcutaneous injection.

To compare the pharmacokinetics of two different concentrations, containing either 40 or 100 IU/ml of short-acting human insulin (Velasulin HM), intermediate-acting human insulin (Insulatard HM), or an insulin mixture (25% short-acting insulin, 75% intermediate-acting insulin; Mixtard HM), three randomized, single-blind, crossover trials were performed using the euglycemic clamp technique. Eighteen healthy volunteers received insulin of either formulation subcutaneously in each of the studies (15 IU Velasulin, 20 IU Insulatard, or Mixtard). The blood glucose levels were maintained constant by glucose infusions. In the trial using Velasulin, the two different insulin concentrations were equivalent regarding the total absorption [area under the curve (AUC) of serum insulin: 126 +/- 28 and 123 +/- 35 mU/l x 12 h for U40 and U100 (mean +/- SD)], but not in regard to the rate of absorption (t max 1.3 +/- 0.4 and 2.4 +/- 1.0 h for U40 and U100). In the case of Insulatard, total absorption was not equivalent (AUC 153 +/- 35 and 128 +/- 37 ml/l x 24 h for U40 and U100), but the rate of absorption was equivalent (t max 4.8 +/- 2.9 and 5.3 +/- 4.6 h). In the Mixtard series, total absorption was equivalent (AUC 142 +/- 32 and 128 +/- 22 mU/l x 24 h), but the rate of absorption was not (t max 2.2 +/- 0.9 and 3.2 +/- 4.2 h for U40 and U100). The glucose requirement was not equivalent in each of the three series.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of previous glycaemic control on the onset and magnitude of cognitive dysfunction during hypoglycaemia in type 1 (insulin-dependent) diabetic patients.

To determine whether the degree of previous glycaemic control may modify cognitive responses to hypoglycaemia, the glycaemic thresholds for, and magnitude of cognitive dysfunction as assessed by P300 event-related potentials as well as subjective and hormonal responses during hypoglycaemia were evaluated. Hypoglycaemia was induced by intravenous insulin infusion in 18 Type 1 (insulin-dependent) diabetic patients, 7 of whom were strictly controlled (HbA1c: 6.3 +/- 0.3%; mean +/- SEM; Group 1) and 11 of whom were poorly controlled (HbA1c: 9.1 +/- 0.4%; Group 2). Within 60 min, mean blood glucose declined from 5.6 and 5.7 mmol/l (baseline) to a nadir of 1.6 and 1.8 mmol/l followed by an increase to 5.6 and 4.3 mmol/l after 120 min in Group 1 and 2, respectively. There was no significant difference between the groups in regard to P300 latency at baseline, but between 50 and 70 min a significant prolongation of this component was noted in Group 2 as compared with Group 1 at blood glucose levels between 1.6 and 2.3 mmol/l (p less than 0.05). The glycaemic thresholds at which a significant increase of P300 latency over baseline was first noted were 1.6 +/- 0.2 mmol/l in Group 1 and 3.5 +/- 0.2 mmol/l in Group 2 (p less than 0.05). The glucose thresholds at which this prolongation was no longer demonstrable were 1.9 +/- 0.1 mmol/l in Group 1 and 3.8 +/- 1.4 mmol/l in Group 2, respectively (p less than 0.05). The glycaemic threshold at which the P300 amplitude was first significantly reduced was 2.2 mmol/l in Group 2, whereas no such reduction was observed in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The effect of etomoxir on insulin sensitivity in type 2 diabetic patients.

Oral application of 50 mg Etomoxir caused a significant rise (33.1%) of insulin-mediated glucose uptake. This was shown in a placebo-controlled, double-blind randomized study in 8 type 2 diabetic patients by using the euglycemic clamp technique. The mean metabolic clearance rate of glucose (MCR) was raised from 4.1 +/- 0.9 mg/(kg.min) to 5.4 +/- 1.2 mg/(kg.min) (x +/- SEM, P = 0.039). Plasma levels of free fatty acids (FFA), glucose counterregulatory hormones, lipids and C-peptide values during the clamps were not different after verum and placebo. We conclude that Etomoxir improves insulin sensitivity in type 2 diabetic patients.

Aged↗

Increased GPIIB/IIIA expression and altered DNA-ploidy pattern in megakaryocytes of diabetic BB-rats.

Hyperactive platelets contribute to angiopathic complications in diabetes mellitus. It is unclear whether the increased platelet function is a primary pathogenetic factor in diabetes or follows vascular injury. Increased platelet size and numbers of glycoprotein receptors on diabetic platelets suggest that thrombopoiesis is altered in diabetes mellitus. For further support of this hypothesis we studied whether megakaryocytes are changed with regard to the DNA-ploidy pattern and the GPIIB/IIIA expression in 10 acute diabetic (AD) and 24 insulin treated diabetic (ITD) BB rats in comparison with 22 diabetes resistant (ND) BB rats. In the AD group megakaryocyte size (P = 0.035) and the modal DNA-ploidy distribution dropped (P = 0.0001) concomitant with increased TNF-alpha activity (P = 0.001). GPIIB/IIIA expression and the peripheral platelet status were unchanged. After 4 weeks of insulin substitution metabolic parameters (glucose, cholesterol, triglycerides) were lowered, but remained still elevated. As compared to the AD group the modal DNA-ploidy pattern reversed, but the relative percentage of 64n megakaryocytes increased 2.3-fold and GPIIB/IIIA expression increased 1.6-fold. Simultaneously, the peripheral platelet count and size increased. From these results we conclude that alterations of the megakaryocyte compartment occur at early onset of diabetes. These changes could reflect a response to increased systemic cytokine production during inflammatory islet cell destruction. The peripheral platelet thrombotic potency increased with insulin treatment. This was associated with an increase of 64n-megakaryocytes with upregulated GPIIB/IIIA expression and could reflect a mitogenic effect of insulin upon the endomitotic cycle of the megakaryocytes.

Animals↗

Assessment of cardiovascular autonomic function: age-related normal ranges and reproducibility of spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses.

To establish normal ranges for assessment of autonomic dysfunction, a battery of cardiovascular reflex tests was performed in 120 healthy subjects aged 15-67 years using a computer-based technique. Tests of heart rate variation (HRV) included 8 measures at rest: coefficient of variation (CV), root mean squared successive difference (RMSSD), spectral analysis of HRV in the low frequency, mid frequency, and high frequency bands in the supine and standing postures; 5 measures during deep breathing: CVb, RMSSDb, Expiration-Inspiration (E-I) difference, E/I ratio, and mean circular resultant of vector analysis; Valsalva ratio, and max/min 30:15 ratio. In addition, the change in systolic and diastolic blood pressure in response to standing and the diastolic blood pressure response to sustained handgrip were determined. The results of all measures, the blood pressure tests excepted, declined significantly with increasing age (r = -0.16 to -0.59; p less than 0.05). Moreover, RMSSD, RMSSDb, and E-I difference decreased considerably with increasing heart rate (r = -0.37 to -0.52; p less than 0.001). The longest and shortest R-R intervals in response to standing were distributed within beats 21-39 and 6-24, respectively. All tests were independent of sex. Log transformation was used to define the age-related lower limits of normal at the 2.3 centile for all tests of HRV, except for the E/I, Valsalva, and max/min 30:15 ratios. The results of these tests had to be analysed using a log(y-1) transformation. The intra-individual reproducibility determined on two consecutive days in 20 healthy subjects and 21 diabetic patients indicated that there were no major differences between the two groups regarding the day-to-day variation of test results, which was highest for the Valsalva ratio. We conclude that: (1) all indices of spectral and vector analyses of HRV are age-dependent and have the advantage of being independent of heart rate; (2) RMSSD, E-I difference, and the 30:15 ratio as it was used previously are not suitable for evaluation of autonomic dysfunction in diabetes; (3) log(y-1) transformation is required to determine age-dependent normal ranges and reproducibility for the three ratios.

Adolescent↗

Prevalence of cardiovascular autonomic dysfunction assessed by spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses at various stages of diabetic neuropathy.

To establish a test battery for the detection and characterization of cardiovascular autonomic neuropathy (CADN) and to evaluate its prevalence, a number of autonomic function tests based on spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses were performed in 261 diabetic patients aged 11-76 years with various stages of peripheral neuropathy. The percentages of abnormal results in the individual tests based on heart rate variation were 6-31% in 115 patients without peripheral neuropathy, 16-45% in 61 patients with subclinical neuropathy, 22-59% in 73 patients with symptomatic peripheral neuropathy, and 67-100% in 12 patients with the latter in conjunction with autonomic symptoms (p < 0.05). The most frequently abnormal indices, each representing a different physiological basis, were the coefficient of variation, low-frequency and mid-frequency power spectrum at rest, mean circular resultant, postural change in systolic blood pressure, and, in particular, the max/min 30:15 ratio and Valsalva ratio. CADN, defined as the presence of > or = 3 abnormalities among these seven parameters was detected in none of 120 control subjects, 13.0% of the patients without peripheral neuropathy, 34.4% of those with subclinical neuropathy, 49.3% of those with symptomatic peripheral neuropathy, and in 100% of the subjects with the latter and concomitant autonomic symptoms (p < 0.05). The overall prevalence of CADN in 103 patients completing all parameters was 46.6%. The corresponding rate of CADN defined as > or = 2 abnormalities among the five tests included in an optimized version of the battery proposed by Ewing and Clarke was 38.8%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Prevalence of cardiovascular autonomic dysfunction assessed by spectral analysis and standard tests of heart-rate variation in newly diagnosed IDDM patients.

OBJECTIVE: To determine the prevalence of cardiovascular autonomic nerve dysfunction in patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) compared with healthy nondiabetic subjects. RESEARCH DESIGN AND METHODS: A battery of cardiovascular reflex tests was performed in 130 newly diagnosed IDDM patients aged 12-40 yr at mean blood glucose levels of 7.2 mM after insulin had been administered for 3-39 days. Age-dependent lower limits of normal of these tests were defined at the 2.3 percentile in 120 nondiabetic subjects. Tests of heart-rate variation (HRV) included the coefficient of variation (C.V.) and the low-frequency (LF), midfrequency (MF), and high-frequency (HF) bands of spectral analysis at rest, HRV during deep breathing (C.V., expiratory-inspiratory ratio, and mean circular resultant), Valsalva ratio, and maximum/minimum 30:15 ratio. In addition, spectral analysis on standing, the change in systolic blood pressure to standing, and diastolic blood pressure response to sustained handgrip were determined in 50 patients. RESULTS: A significantly higher percentage of abnormal test responses in the diabetic group compared with the control group was noted for power spectrum in the LF band (7.3 vs. 0.8%, P less than 0.05) and MF band (10.6 vs. 0%, P less than 0.001) at rest and HF band on standing (10.0 vs. 0.9%, P less than 0.05), maximum/minimum 30:15 ratio (25.4 vs. 5.0%, P less than 0.001), and Valsalva ratio (17.5 vs. 4.2%, P less than 0.001). There were no significant differences between both groups in regard to the remaining parameters. Ten (7.7%) diabetic patients but none of the nondiabetic subjects had cardiovascular autonomic neuropathy defined by the strict criterion of abnormal results in more than three of six tests (P less than 0.001). In addition, 12 (9.2%) patients but only 2 (1.7%) control subjects had abnormal results in two of six tests (P less than 0.01). CONCLUSIONS: Cardiovascular autonomic nerve dysfunction is relatively common in newly diagnosed IDDM patients after correction of the initial metabolic imbalance. A combination of tests based on spectral and conventional analysis of HRV appears suitable for detection of early abnormalities in autonomic function in diabetes.

Adolescent↗

Reduced platelet thromboxane formation after long-term administration of a dihydropyridine calcium channel blocker: a prospective, double-blind, placebo-controlled study with nitrendipine in borderline hypertensive patients with IDDM-type diabetes mellitus.

Twenty-nine IDDM patients with borderline hypertension were randomly allocated to placebo or nitrendipine treatment. Nitrendipine was given orally at a dosage of 20 mg once daily over 4 weeks. Stimulated platelet thromboxane formation at rest and after standardized, non exhausting exercise was measured by standard methods. In addition, plasma levels of platelet factor 4 and aggregation responses to collagen and ADP were determined. In the treatment group thromboxane formation after stimulation with collagen (0.3 and 1.0 micrograms/ml) and 1 mM arachidonic acid (AA) was reduced in the resting state. Exercise induced change of thromboxane synthesis in response to 1.0 micrograms/ml collagen was significantly lower as compared to placebo (p < 0.05). In parallel, PF4 plasma levels were significantly lowered (p < 0.05). Whole blood aggregation after collagen stimulation (1.0 micrograms/ml) was reduced after 4 weeks of nitrendipine treatment, but ADP (5 microM) induced aggregation was not. These effects of nitrendipine were not seen in platelet rich plasma. In conclusion long-term nitrendipine treatment may inhibit collagen dependent platelet activation in the blood of diabetic patients with borderline hypertension.

Adenosine Diphosphate↗