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Biomedical subjects

S Piazzi

Publications and source records attributed to S Piazzi.

At least 19 recordsLinked to original sources

CYP21 analysis and phenotype/genotype relationship in the screened population of the Italian Emilia-Romagna region.

OBJECTIVES: We have genotyped the patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency identified from March 1980 to December 1997 through a combined program of neonatal screening and case survey in the Emilia-Romagna Region (Italy). We have also analysed retrospectively the possible advantages of genotypical neonatal classification. DESIGN: A 'phase A' of screening and clinical monitoring (March 1980-September 1983 and March 1991-December 1997) and a 'phase B' of clinical monitoring only (October 1983-February 1991) were taken into account. PATIENTS: A total of 61 patients (20 salt wasting, nine simple virilizing and 32 nonclassical forms) were genotyped, HLA typed and hormonally tested to understand better the genotype/phenotype relationship and the epidemiology and geographical distribution of associated mutations. The fully genotyped patients were classified into four mutation groups according to the degree of enzymatic activity ('null' and 'A' to 'C'). RESULT: The most frequent genotype alterations were deletion (24.1% classical, 3.3% nonclassical forms), large gene conversion (9.2% classical, 1.7% nonclassical forms), In2 splice (27.7% classical, 15.0% nonclassical forms), I172N (5.5% classical, 10.0% nonclassical forms), V281L (3.7% classical, 43.3% nonclassical forms), P453S (5.0% nonclassical forms). A significant difference (chi2 = 5.101; P < 0.025) in the distribution of classical genotypes was found in Romagna (south-east; incidence 1 : 7437 newborns) compared to Emilia (north-west; incidence 1 : 25 090 newborns). Two putative new mutations were found in our population. Little discrepancy was found between genotype and phenotype. CONCLUSIONS: The high frequency of genotypes 'null' or 'A' in the 'phase A' vs. 'phase B' of our study confirms the usefulness of neonatal screening in preventing the death of male patients with salt wasting forms. The substantial similarity in the mutational spectrum of classical forms found in our study, based on the detection of all the classical patients of a specific area, leads us to believe that the distribution of mutations is due to the inherent characteristics of the gene locus, and that regional effects play a minor role. Prompt neonatal genotyping can be of valuable diagnostic assistance in neonatal screening for the confirmation of the diagnosis in newborns with moderately elevated 17 hydroxyprogesterone levels.

Adolescent↗

Lipid peroxidation and antioxidant status in adults receiving lipid-based home parenteral nutrition.

BACKGROUND: Infusion of lipid emulsions rich in polyunsaturated fatty acids (PUFAs) may increase lipid peroxidation, which is counteracted mainly by superoxide dismutase (SOD) (a zinc-, copper-, and manganese-dependent enzyme), selenium-dependent glutathione peroxidase (Se-GSHPx), and alpha-tocopherol. OBJECTIVE: We investigated lipid peroxidation and antioxidant status in patients receiving home parenteral nutrition (HPN) providing variable amounts of a lipid emulsion rich in PUFAs, and alpha-tocopherol, zinc, copper, and manganese as recommended by the American Medical Association, and no selenium. DESIGN: Serum malondialdehyde, plasma alpha-tocopherol, selenium, Se-GSHPx, PUFAs, and red blood cell Se-GSHPx and SOD were evaluated in 12 patients and in 25 healthy control subjects. Malondialdehyde was also assessed in a group of 40 healthy control subjects. RESULTS: Patients had significantly higher concentrations of malondialdehyde and SOD and lower alpha-tocopherol concentrations and selenium nutritional status. Linear regression analysis showed that malondialdehyde was associated with the daily PUFA load (r=0.69, P< 0.03) and with plasma alpha-tocopherol (r=-0.59, P< 0.05), but stepwise multiple regression analysis confirmed only the association between malondialdehyde and alpha-tocopherol; plasma alpha-tocopherol was associated with the daily PUFA load (r=-0.65, P< 0.04) and with the duration of HPN (r=-0.74, P< 0.02). CONCLUSIONS: In HPN patients, the peroxidative stress due to lipid emulsions rich in PUFAs is counteracted primarily by alpha-tocopherol. The dosages of alpha-tocopherol, zinc, copper, and manganese recommended by the American Medical Association appear sufficient to sustain SOD activity but inadequate to maintain alpha-tocopherol nutritional status. HPN formulations should be supplemented with selenium.

Adolescent↗

[Results of screening of congenital hypothyroidism and iodine excess in neonatal age].

We evaluated the distribution of TSH levels on dried blood spots (Delfia system-threshold value for recall 20 microU/ml) in 27,282 consecutive samples examined during 1993, in the Emilia-Romagna region. We also evaluated, by questionnaire, the frequency of iodine disinfection in the perinatal period in all centers that do blood spots. We also evaluated the distribution of TSH spot values according to the localization of the center in endemic or not endemic area of the region. Among the parameters we considered, only the sampling day (p < 0.02) and the maternity center (p < 0.0001) showed a significant influence on TSH spot values. With regard to the questionnaire, the centers which habitually used iodine disinfection in obstetrics (20/28) showed significantly higher percentages of TSH values over 10 microU/ml than the centers which did not use (3/28) or rarely used (4/28) this type of disinfection (p < 0.0001). The only center which used regular iodine disinfection of umbilical cord in all newborns, showed a percentage of TSH values over 10 microU/ml (25.8%) and a recall rate (2.5%) significantly higher than all other centers (p < 0.0001).

Anti-Infective Agents, Local↗

Hyperhomocyst(e)inemia and a common methylenetetrahydrofolate reductase mutation (Ala223Val MTHFR) in patients with inherited thrombophilic coagulation defects.

To assess whether certain abnormalities of the sulfated amino acid metabolism are associated with the occurrence of thromboembolic events in patients with inherited thrombophilic conditions, the levels of homocyst(e)ine, before or after methionine load, and the presence of the Ala223Val substitution in the 5,10-methylenetetrahydrofolate reductase (MTHFR) were evaluated in 119 subjects with a congenital single thrombophilic condition (type I deficiency of antithrombin n = 10, protein C n = 24, protein S n = 16; activated protein C resistance due to factor V Leiden mutation n = 69). Sixty-three subjects had experienced at least one documented thrombotic event, while the remaining 56 subjects were still free from any thrombotic symptom. Our results show that (1) high homocyst(e)ine levels, either in fasting condition or after methionine load, were not more frequent in subjects with inherited thrombophilic alterations (14.4%) than in normal control subjects (10% by definition) and (2) the frequency of hyperhomocyst(e)inemia was similar in thrombophilic subjects, who already have (14.3%) or have not (14.6%) experienced thrombotic events. As regards the MTHFR mutation, the homozygous condition was present in 23.2% of the thrombophilic patients versus 17.5% in the control subjects, a nonsignificant difference. The mutation was slightly more frequent in those thrombophilic subjects who had suffered a thrombotic episode (25.5%) versus those with no thrombosis (20.8%), with odds ratios of 1.61 (confidence interval (CI) = 0.58-4.52) and 1.24 (CI = 0.42-3.43), respectively. These differences were also nonsignificant. It is concluded that in subjects with inherited thrombophilias, a condition of hyperhomocyst(e)inemia "per se" is not a factor increasing the risk of thrombosis. The risk enhancement conferred by the MTHFR mutation, if any, seems to be slight or limited, and its significance could be ascertained only in a large multicenter trial.

Adult↗

Congenital adrenal hyperplasia: neonatal mass screening compared with clinical diagnosis only in the Emilia-Romagna region of Italy, 1980-1995.

OBJECTIVE: Comparative study of the incidence of classic 21-hydroxylase deficiency congenital adrenal hyperplasia (21ase-def CAH) and clinical findings of affected infants diagnosed via newborn screening versus case survey only in the Emilia-Romagna region of Italy. METHODS: Neonatal mass screening (from March 1980 to September 1983-Period A, and from March 1991 to August 1995-Period C) and case survey study (from 1980 to June 1995; case survey alone from October 1983 to February 1991--Period B) were performed by the Regional Referral Center for Neonatal Screening for Endocrine-Metabolic Disease with a laboratory (Central Laboratory, S. Orsola Hospital, Bologna) and clinical (First Pediatric Clinic, University of Bologna, S. Orsola Hospital, Bologna) component. A population-based sample of 420 960 newborns consecutively born in the Emilia-Romagna region from March 1980 to August 1995 were studied. Spot 17-OH-progesterone (nmol/L blood) was tested by the radioimmunoassay method after sample extraction during Period A and by fluoroimmunometric time resolved method without sample extraction during Period C. Serum 17-OH-progesterone (ng/dL or nmol/L) was tested by the radioimmunoassay method (Diagnostic Product Corporation Kit, Los Angeles, CA). The case survey was performed by means of a questionnaire sent to all regional centers dealing with pediatrics, neonatology, endocrinology, and pediatric surgery. RESULTS: Thirteen classic 21ase-def CAH were diagnosed by means of neonatal screening (combined A and C periods). One true and one questionable false-negative cases were identified. The incidence of classical 21-hydroxylase deficiency for the white population was 1:15 518 (95% confidence limits 1:9249-1:28 400) by neonatal screening plus case survey, 1:18 105 (95% confidence limits 1:10 365-1:35 041) by neonatal screening alone and 1:25 462 (95% confidence limits 1:12 925-1:59 043) by case survey alone. The sensitivity and specificity of screening for classic CAH were 83% and 99.8% for Period A and 90% and 99.2% for Period C, respectively. The percentage of salt-wasting forms and the male/female ratio were higher during the neonatal screening period than during the case survey only. Sixty-one percent of classic CAH patients benefited from a prompt diagnosis. Nonclassical 21ase-def CAH cases detected via screening and case survey were also reported. CONCLUSIONS: Even in a region with adequate neonatal services, clinical diagnosis alone of classic CAH might be delayed or misinterpreted and salt-wasting crises could cause neonatal deaths. CAH screening is thus an effective tool for diagnosing affected male infants without a family history of CAH and for preventing salt loss. However, to achieve maximal benefit from screening, quick procedures are necessary for notification of positive results and beginning prompt treatment. The possibility of false-negative cases indicates that clinical observation should never be abandoned, even with ongoing screening programs.

17-alpha-Hydroxyprogesterone↗

[Models of the organization of neonatal screening].

The authors evaluate the different organizational strategies of a congenital hypothyroidism screening program. Positive and negative aspects of laboratory screening tests (TSH only, T4-supplemental TSH, TSH and T4), organization strategies (centralization or decentralization), recall and first follow-up criteria are examined. The authors consider that the necessity for an early diagnostic confirmation can be associated with a precise etiologic diagnosis and an evaluation of the prenatal severity of congenital hypothyroidism factors. Some European and North-American experiences are compared with the activity of a regional Italian screening center.

Congenital Hypothyroidism↗

Early and late changes in fasting and absorptive plasma amino acids and ammonia after distal splenorenal shunt in cirrhosis.

Levels of plasma amino acids, ammonia, glucagon and insulin and their 5-hr responses to a protein feeding were evaluated before and sequentially (3 mo and 1 yr) after distal splenorenal shunt in 10 patients with cirrhosis belonging to Child-Pugh's class A or B. An index of glucagon effectiveness (plasma glucose/glucagon) was also calculated. These parameters were related to liver test results, portal vein diameter and mental state, and they were compared with those found in seven patients undergoing sclerotherapy of esophageal varices with comparable liver function (control group). Liver test results and levels of plasma insulin did not change in either group. Shunt significantly increased levels of fasting tyrosine, methionine, ornithine, arginine, histidine, ammonia and glucagon with respect to the control group; it also significantly decreased levels of leucine, valine, glucagon effectiveness and portal vein diameter. The elevation of levels of tyrosine, ammonia and the sum of arginine and ornithine was correlated directly with the increase in glucagon and inversely with the decline in glucagon effectiveness. Tyrosine increase was also correlated with the reduction of portal vein diameter. One shunted patient showed mild hepatic encephalopathy. Protein feeding did not worsen the mental state of patients before and after the operation. Surgery significantly increased the 5-hr response to the meal of gluconeogenic amino acids; its rise was again correlated with the changes in glucagon plasma levels and effectiveness. Although the absorptive levels of plasma ammonia were significantly higher 1 yr after surgery, its 5-hr response barely rose. In cirrhotic patients with a relatively preserved liver function, distal splenorenal shunt progressively worsened the fasting plasma profile of nitrogen compounds and the response to protein ingestion of gluconeogenic amino acids. The decline of portal blood flow and glucagon effectiveness may be causal factors. Despite this, the "cerebral" tolerance to a moderate oral load of protein was not reduced by surgery.

Adult↗

Improved high-performance liquid chromatographic method for the determination of coenzyme Q10 in plasma.

Coenzyme (Co) Q10 was dissociated from lipoproteins in plasma by treatment with methanol and extraction with n-hexane. Subsequent clean-up on silica gel and C18 solid-phase extraction cartridges with complete recovery (99 +/- 1.2%) produced a clean extract. High-performance liquid chromatographic (HPLC) separation was performed on a C18 reversed-phase column. Three simple, rapid procedures are presented: HPLC with final UV (275 nm) detection, a microanalysis utilizing a three-electrode electrochemical detector and a microanalysis with column-switching HPLC and electrochemical detection. The methods correlate very well with classical ethanol-n-hexane extraction with UV detection. The identity and purity of the Co Q10 peak were investigated and the resulting methods were concluded to be suitable for total plasma Co Q10 determination. The average level in healthy subjects was 0.80 +/- 0.20 mg/l; the minimum detectable Co Q10 plasma level was 0.05 and 0.005 mg/l for UV and electrochemical detection, respectively. The methods were applied to many samples and the plasma Co Q10 reference values for healthy subjects, athletes, hyperthyroid, hypothyroid and hypercholesterolaemic patients are given.

Chromatography, High Pressure Liquid↗

Myocardial metabolic and hemodynamic effects of a sustained intravenous infusion of nifedipine with and without metoprolol in patients with unstable angina.

We tested the usefulness of a sustained intravenous infusion of nifedipine and a combination of nifedipine and metoprolol in the early management of 14 patients with unstable angina pectoris. After a 24-hour run-in period, nifedipine was titrated in a stepwise fashion (mean dose 27 +/- 7 micrograms/min). After nifedipine treatment coronary blood flow increased from 150 +/- 66 to 183 +/- 74 ml/min (p less than 0.05), whereas double product, myocardial oxygen consumption, and both arterial and coronary sinus (nor)epinephrine levels were unchanged. Myocardial lactate uptake increased from 3.4 +/- 26.1 to 31.3 +/- 26.6 mumol/min (p less than 0.005) and free fatty acid uptake from 7.2 +/- 22.1 to 34.5 +/- 33.7 mumol/min (p less than 0.05). A small nonsignificant improvement in amino acid metabolism was observed. Metoprolol was added in seven patients and led to a decrease in double product (-2.2 +/- 1.6 x 10(3); p less than 0.01) and myocardial oxygen consumption (-3.2 +/- 3.8 ml/min; p less than 0.05). The lactate uptake/oxygen uptake ratio increased by 18% after metoprolol (p = NS). The number of episodes of chest pain decreased from 2.4 +/- 1.1/24 hours to 0.1 +/- 0.2 in the nifedipine group and from 2.9 +/- 1.1/24 hours to 0.3 +/- 0.5 in the nifedipine plus metoprolol group (both p less than 0.01). We conclude that in the acute phase of unstable angina, intravenous nifedipine can be carefully titrated to improve coronary blood flow and oxidative metabolism. The addition of metoprolol is also associated with a reduction in myocardial oxygen demand. This treatment results in significant hemodynamic stability.

Adult↗

Nutritional status of patients undergoing ileal pouch-anal anastomosis.

The nutritional consequences of total colectomy and ileal pouch-anal anastomosis (IPAA) were assessed by evaluating 36 patients at the end of the defunctionalised stage (DS group) and 18 patients with recanalised IPAA (IPAA group). The changes in protein-calorie and zinc status occurring after the closure of the diverting ileostomy were evaluated also in 11 patients assessed both during the DS and the IPAA stage. The results were compared with those observed in 14 patients who underwent a Brooke-type permanent ileostomy (PI group). In the DS group there were protein-calorie malnutrition in 50% of cases characterised by body weight, TSF and AMC values lower than normal associated with normal serum protein levels; severe salt and water depletion with secondary aldosteronism in 90%; normal calcium-phosphorus balance in all but few cases, low values of parameters related to vitamin D and K, Fe, Zn and Cu status in 6-25% of cases and normal folate status. In the IPAA group all the anthropmetric parameters improved significantly after the closure of the protective ileostomy, but muscle mass (AMC) remained lower than normal in 40% of cases; mild salt depletion (urinary Na K ratio between 1 and 2) was observed in 1 3 of cases and of severe degree (urinary Na K < 1 ) in 20%; lower serum Zn occurred in 60% of patients probably due to greater requirements of the metal, secondary to increased muscle protein synthesis; parameters of calcium-phosphorus balance, vitamin D and K, folate, Fe and Cu status, were normal in almost all the cases. In the PI group, protein-calorie and salt and mineral nutritional status were similar to those of the IPAA group, whereas Zn status was normal in all the patients and erythrocytes folate levels and prothrombin time were significantly lower than in the IPAA group. These last two results might be explained by the different characteristics of the small bowel flora occurring in the two types of ileostomy.

Journal Article↗

Role of gluconeogenesis from amino acids in determining fasting and absorptive levels of plasma ammonia in cirrhosis.

The aim of this study was to evaluate the contribution of gluconeogenesis from amino acids in the development of fasting and absorptive hyperammonemia in cirrhosis. Somatostatin (SRIF), which is known to inhibit the hepatic disposal of gluconeogenic amino acids, was administered in a continuous infusion (500 micrograms/h) for 90 min before and 5 h after a protein meal (240 g of meat) in 11 overnight fasting patients. Plasma glucagon, insulin, gluconeogenic amino acids (GAA: alanine, serine, glycine, and threonine) and ammonia (NH3) were evaluated before the infusion, immediately before, and at 1, 3, and 5 h after the meal. As control study, the same protocol was randomly repeated in a different day with saline infusion. During the latter, a direct correlation was found between fasting glucagon and ammonia (r = 0.68; p less than 0.05). Fasting glucagon, insulin, and NH3 did not change, whereas alanine (p less than 0.05) and the GAA sum decreased (p less than 0.01). When SRIF was infused, fasting glucagon (p less than 0.05), insulin (p less than 0.05), and NH3 (p less than 0.05) decreased. Alanine did not change, and GAA sum increased (p less than 0.02). No correlations were found by plotting changes in glucagon or GAA sum and NH3. After the meal, SRIF infusion abolished the plasma response of glucagon and markedly reduced that of insulin, so that their area under the curve (AUC0-5) were reduced (p less than 0.005, for both), with respect to control study. Moreover, the AUC0-5 of alanine (p less than 0.005) and GAA sum (p less than 0.005) were increased, suggesting a reduced disposal of these compounds. In spite of this, the meal-induced early increase and the AUC0-5 of plasma NH3 observed during SRIF and saline infusion did not differ. Our results do not confirm the importance of gluconeogenesis from alpha-amino-nitrogens in determining the fasting ammonemia of cirrhosis, and suggest that this metabolic pathway does not significantly influence the protein meal-induced exacerbation of plasma ammonia.

Adult↗

Urinary zinc excretion in Crohn's disease.

In order to study the reliability of urinary zinc levels as an index of zinc metabolism and status in Crohn's disease, we evaluated plasma and urinary zinc concentrations, urinary 3-methylhistidine excretion, and Crohn's disease activity index (CDAI) in 42 patients affected by Crohn's disease. Plasma zinc correlated directly with albuminemia (P = 0.01) and inversely with CDAI (P = 0.001). Urinary zinc excretion correlated with urinary 3-methylhistidine (P = 0.001) and plasma zinc levels (P = 0.01), and inversely with CDAI (P = 0.05). However, from multiple regression analysis, it was found that zincemia is influenced by CDAI and not by albumin, whereas zincuria is related to urinary 3-methylhistidine and plasma zinc, and not to CDAI. Our conclusion is that, in Crohn's disease, zincuria can be an index of zinc status when used together with measurements of lean body mass and turnover and factors influencing plasma ultrafiltrable zinc fraction.

Adolescent↗

Effect of different intravenous nutrients on metabolic changes in short-term fasted man.

It is well documented (1-3) that a balanced use of nutritive solutions is important to maintain metabolic homeostasis and a better control of nutrient flux in fasting patients. In this trial, 10 healthy males, aged 30-50 years, fasted for 12 h, were subjected to intravenous nutrient loads in three separate trials. In the first trial they received only a fat emulsion, in the second fat emulsion and L-amino acid solution, and in the third fat emulsion, L-amino acid solution and glucose solution, 240 and 480 min after intravenous infusion plasma triglycerides, serum cholesterol, free fatty acids, lactate, glucose and plasma amino acids were determined. Significant biochemical changes were detected with regard to triglycerides, lactic acid, free fatty acids, alanine, glutamine, lysine and proline concentrations, depending on the different mixtures utilized.

Adult↗

Blood coagulation changes in homocystinuria: effects of pyridoxine and other specific therapy.

The aim of this study was to investigate the blood coagulation changes in three patients with homocystinuria, in baseline condition and during therapy. At baseline, antithrombin III activity and factor VII levels were reduced in all three patients; antithrombin III protein and protein C antigen were also slightly lowered in one patient, and factor X in another. beta-Thromboglobulin, a measure of platelet activation, was increased in one case. During pyridoxine treatment, antithrombin III activity was rapidly restored to normal; factor VII increased and beta-thromboglobulin decreased. These data suggest that, in addition to platelet activation, abnormalities of blood clotting, and particularly reduction of antithrombin III, may play a role in the thrombotic tendency associated with homocystinuria. The nature of these clotting alterations is still uncertain, but their improvement during active metabolic treatment suggests that the defect in amino acid transsulfuration of homocystinuria may directly affect synthesis or activity of some liver-dependent clotting factors.

Adolescent↗

Effects of somatostatin on plasma ammonia and amino acid profile during fasting and after protein feeding in cirrhotic patients.

The effects of somatostatin on fasting and absorptive plasma ammonia and amino acids were studied in 12 cirrhotic patients. They received a 6 h intravenous infusion of somatostatin (500 micrograms/h) or saline, starting 90 min before protein feeding. During the fasting period somatostatin significantly reduced plasma ammonia (-18%) and total tryptophan (-39%), increased plasma leucine (+19%), isoleucine (+17%), glutamine (+22%), glycine (+13%), arginine (+14%) and lysine (+12%), and prevented the significant fall of phenylalanine (-8%), tyrosine (-6%), alanine (-8%) and threonine (-9%) seen with saline. The percent changes in ammonia and glutamine concentrations were inversely correlated (r = -80; p less than 0.001) After protein ingestion, somatostatin slowed the maximal plasma increase in ammonia and alpha-nitrogens by at least two hours, but their total 5 h plasma response was not reduced, and even, in some instances, significantly increased (valine, leucine, glutamine, alanine and serine) with respect to saline. The results suggest that in fasting cirrhotics somatostatin reduces plasma ammonia, probably through an impaired intestinal ammoniogenesis from circulating precursors, and inhibits the disposal of branched chain, aromatic (except tryptophan) and gluconeogenic amino acids. Furthermore, it delays, but does not reduce, the plasma increase in nitrogen after protein ingestion.

Adult↗

Effect of 'physiological' doses of triiodothyronine replacement on the hormonal and metabolic adaptation to short-term semistarvation and to low-calorie diet in obese patients.

In four groups of obese patients matched for Body Mass Index (BMI), we studied the effects of different 3-week semi-starvation treatments followed by an 8-week hypocaloric (1008 kcal, protein 20%, carbohydrate 40%) diet with or without low doses of T3 therapy. Dietary intake (formula diet) in the semi-starvation period was 480 kcal, with 66 g protein (P) and 51 g carbohydrate (CHO) in groups I and III and with 33 g P and 84 g CHO in groups II and IV. Moreover, groups III and IV were given low doses (20 micrograms twice a day) of T3 while groups I and II received a placebo. During semi-starvation periods, a similar fall in BMI values was found in all groups, while during the low-calorie diet, T3-treated patients showed the greater BMI reduction. During semi-starvation, nitrogen balance was significantly more negative in low-protein than in high-protein-treated groups; differences between T3-treated (III and IV) and control (I and II) groups were not significant over this relatively short treatment period. No differences in 24 h urinary 3-methylhistidine or alanine excretion were evident between the four groups. During the entire period of study, daily urine creatinine excretion did not change in any group. In conclusion, in our study low-dose T3 therapy was seen to favour weight loss during low-calorie diet although negative effects on protein metabolism were not excluded, particularly when relatively small amounts of protein were administered.

Adult↗