Search PubMed⌕ Search

Biomedical subjects

S Yamada

Publications and source records attributed to S Yamada.

At least 289 records · Page 16Linked to original sources

Usefulness of early diastolic flow propagation velocity measured by color M-mode Doppler technique for the assessment of left ventricular diastolic function in patients with hypertrophic cardiomyopathy.

Flow propagation velocity (FPV) of left ventricular (LV) filling flow has been shown to be a useful index for the evaluation of LV diastolic function, which is relatively independent of preload in myocardial infarction and dilated cardiomyopathy, but the usefulness of FPV for hypertrophic cardiomyopathy (HCM) has not yet been determined. In 23 HCM patients and 26 control subjects, peak transmitral flow velocities in early diastole (E) and during atrial contraction (A), E/A ratio, deceleration time of E velocity, and isovolumic relaxation time were measured with the conventional Doppler technique, and FPV was measured from color M-mode Doppler images of LV filling flow. The time constant of LV isovolumic pressure decay (tau) was measured by a micro-manometer-tipped catheter in all HCM patients and 13 control subjects. Flow propagation velocity was significantly lower and deceleration time was significantly greater in HCM patients than in the control subjects, though no significant differences were observed in the other noninvasive indexes. Tau was significantly prolonged in HCM patients compared with that of control subjects (54+/-12 cm/s and 32 +/-7 cm/s, respectively; P<.0001). While the conventional indexes did not correlate with tau among the 36 patients in whom invasive studies were performed, FPV correlated well with tau (r = -0.76, P<.0001). Flow propagation velocity is a useful noninvasive index for the assessment of LV diastolic function in patients with HCM.

Adolescent↗

Endosseous titanium implants as anchors for mesiodistal tooth movement in the beagle dog.

The purpose of this study was to determine the anchorage potential of titanium implants (Branemark; 3.75 x 7 mm) with the use of a sectional arch wire technique for orthodontic mesiodistal tooth movement, as assessed by the osseointegration of implants and tooth movement. Two implants were surgically placed in healed mandibular extraction sites of the second and third premolars on each side in 4 adult male beagle dogs. The implants were surgically uncovered 18 weeks later, and second-stage abutments with soldered edgewise tubes were attached. Segmented edgewise rectangular archwires (0.017 x 0. 025 inch) with a T-loop or an L-loop were placed between the implants and the fourth premolars on both sides as the anchorage unit. One segment in each dog served as a loaded side, and the archwire was calibrated to produce 200 g of lateral force on the fourth premolar. The contralateral segment served as an unloaded side and was not subjected to orthodontic force. Sectional wires were activated biweekly 24, 28, 28, and 32 weeks, respectively, depending on the magnitude and the appearance of mesial tipping movement of the fourth premolar. After mandibular impressions were taken to measure the distance between the first molar and the fourth premolar, the animals were euthanized and dissected mandibles were prepared. The specimens were then embedded in polyester resin and cut to take backscattered electron images. On the basis of these images, the percentage of peri-implant bone volume was calculated and defined as an index of osseointegration. The differences between the initial and final fourth premolar to first molar distances varied (7.40, 8.85, 10.50, and 3.30 mm) on the loaded side, whereas the unloaded side showed no movement. Not only was there no statistical difference in the percent of peri-implant bone volume between the loaded and unloaded sides, but there was also no statistical difference between the compression and tension sides in both loaded and unloaded implants, which suggests that the implants maintained rigid osseointegration. In conclusion, the present study demonstrated that endosseous titanium implants can function as anchors for long-term orthodontic mesiodistal movement.

Alveolar Process↗

Serum 4-hydroxy-2-nonenal-modified albumin is elevated in patients with type 2 diabetes mellitus.

4-Hydroxy-2-nonenal (HNE) is one of the major lipid peroxidation products with cytotoxic and mutagenic activity. It further reacts with protein residues such as histidine to generate stable Michael adducts. To evaluate the status of oxidative stress in the serum of type 2 diabetes mellitus, we constructed a sandwich enzyme-linked immunosorbent assay to measure serum HNE-modified albumin by the use of a specific monoclonal antibody (HNEJ-2) against HNE-histidine adducts as well as an antibody against human serum albumin. Serum of type 2 diabetes outpatients revealed significantly higher levels of HNE-modified albumin (736.1 +/- 34.2 pmol/ml, n = 54) than the matched nondiabetics (611.4 +/- 39.1 pmol/ml, n = 30; means +/- SEM; p = 0.018). However, no significant correlation was observed in diabetic outpatients between the levels of HNE-modified albumin and clinical parameters such as fasted blood glucose, HbA1c, diabetes duration, or complications. Our data demonstrated the increased formation of serum HNE-modified albumin in type 2 diabetic outpatients in the milieu between liver and vascular lumina, indicating the presence of oxidative stress.

Aged↗

Fructooligosaccharide consumption enhances femoral bone volume and mineral concentrations in rats.

We examined whether the enhanced mineral absorption resulting from fructooligosaccharide (FOS) consumption affects femoral bone structure and mineral concentrations, using histomorphometrical and X-ray microanalysis. Male Wistar rats (n = 16; 42 d old) were divided into two groups, a control group (n = 8) and a FOS group (5 g/100 g FOS in the diet, n = 8). After a 3-d adaptation period, constant amounts of calcium (95 mg/d) and magnesium (8 mg/d) were fed to the rats in each group, using a pair-feeding protocol. At age 60 d, a 3-d metabolic study was initiated. Calcium and magnesium absorptions were calculated. The rats were then killed, and the right femur was embedded in polyester resin. The distal metaphysis was sagittal-sectioned, and the middle of the diaphysis and neck were cross-sectioned. Calcium, magnesium and phosphorus concentrations in the three samples were then measured. Calcium and magnesium absorptions were significantly greater in FOS-fed rats. Trabecular bone volume at the metaphysis and bone volume at the neck of the femur in FOS-fed rats were also significantly greater than those in control rats. The mineral concentration (Ca, Mg and P) in each region of the bone surface was greater in FOS-fed rats. There was a significant relationship between absorbed calcium and calcium concentrations in bone (r = 0.722, P < 0.001), and a similar relationship was found for magnesium (r = 0.720, P < 0.001). These results suggest that the enhanced calcium and magnesium absorption due to FOS consumption might enhance femoral bone volume and mineral concentrations.

Absorption↗

Expression of the PIP aquaporin promoter-MipA from the common ice plant in tobacco.

The reasons for the presence of a multitude of plasma membrane-localized water channels (PIP aquaporins) in plants may be functional differences in water (or other solute) transport, or in developmental, environmental or tissue-specific regulation of expression. We compared tissue- and cell-specific expression of McMipA, an abundantly expressed PIP from the common ice plant (Mesembryanthemum crystallinum), with that of the previously characterized McMipB [Yamada et al. (1997) Plant Cell Physiol. 38: 1326]. The activity of a 2.2 kb DNA fragment containing the promoter region of McMipA in a fusion with the GUS coding region was studied in transgenic tobacco. The McMipA promoter was active in pericycle and cortex cells in roots and in phloem-associated cells and cells surrounding the pericycle in shoots. In green leaves, mesophyll cells and the minor veins showed GUS activity, but the major veins did not. In floral tissues, GUS activity was observed in the pistil and anthers of immature buds and the tip of the mature pistil and pollen. Neither the apical meristem nor root tip showed any GUS activity. The differences in tissue specificity between the McMipA and McMipB promoters indicated that the two PIPs, MC-MIPA and MC-MIPB, serve different functions in plants.

Aquaporins↗

Sequential changes of arterial oxygen tension in the supine position during one-lung ventilation.

UNLABELLED: To investigate how surgical positions affect the severity and progress of hypoxemia during one-lung ventilation (OLV), we studied 33 adult patients undergoing right thoracotomy with left OLV. The patients were divided into three groups according to the positions during surgery as follows: the supine position (SP) group (n = 11), the left semilateral decubitus position (LSD) group (n = 9), and the left lateral decubitus position (LLD) group (n = 13). Analysis of arterial blood gases was sequentially determined every 5 min for 30 min during OLV (fractional ratio of inspiratory oxygen = 1.0) in each position. OLV was promptly terminated and switched to bi-lung ventilation if Spo2 declined to 90%. Pao2 progressively decreased with time in all three groups (P < 0.01). The incidence of termination of OLV within 30 min was higher in the SP group (82%), compared with that in the LSD (11%) and LLD (8%) groups (P < 0.01). Final Pao2 (65+/-12 mm Hg, mean +/- SD, P < 0.01 versus LLD, P < 0.05 versus LSD) and SaO2 (91%+/-4%, P < 0.01 versus LLD and LSD) at the termination of OLV in the SP group were the lowest. There was no difference between these values in the LSD and LLD groups (128+/-54 mm Hg, 96%+/-2%, and 167+/-69 mm Hg, 97%+/-4%, respectively) 30 min after the start of OLV. The time for Pao2 to decrease to 200 mm Hg calculated from each regression curve was 354 s in the SP group, 583 s in the LSD group, and 798 s in the LLD group. The time for Pao2 to decline to 100 mm Hg was 794 s in the SP group. In the regression curves of the LSD and LLD groups, the Pao2 did not decrease to 100 mm Hg. Heart rate was slow at baseline in the SP group (P < 0.05 versus LSD), but other hemodynamic variables did not differ among the three groups throughout this study. The LSD was as effective as the LLD in avoiding life-threatening hypoxemia during OLV. IMPLICATIONS: Close observation and prompt counteractions including termination of one-lung ventilation (OLV) are crucial for patients under OLV in the supine position, because life-threatening hypoxemia frequently occurs approximately 10 min after starting OLV, even under 100% oxygen inhalation. The left semilateral decubitus position was as effective as the left lateral decubitus position in avoiding life-threatening hypoxemia during OLV.

Blood Gas Analysis↗

Carbon dioxide absorbents containing potassium hydroxide produce much larger concentrations of compound A from sevoflurane in clinical practice.

UNLABELLED: We investigated the concentrations of degraded sevoflurane Compound A during low-flow anesthesia with four carbon dioxide (CO(2)) absorbents. The concentrations of Compound A, obtained from the inspiratory limb of the circle system, were measured by using a gas chromatograph. In the groups administered 2 L/min fresh gas flow with 1% sevoflurane, when the conventional CO(2) absorbents, Wakolime(TM) (Wako, Tokyo, Japan) and Drägersorb(TM) (Dräger, Lübeck, Germany), were used, the concentrations of Compound A increased steadily from a baseline to 14.3 ppm (mean) and 13.2 ppm, respectively, at 2 h after exposure to sevoflurane. In contrast, when the other novel types of absorbents containing decreased or no potassium hydroxide/sodium hydroxide, Medisorb(TM) (Datex-Ohmeda, Louisville, CO) and Amsorb(TM) (Armstrong, Coleraine, Northern Ireland), were used, Compound A remained at baseline (<2 ppm) throughout the study. In the groups administered 1 L/min fresh gas flow with 2% sevoflurane, Wakolime(TM) and Drägersorb(TM) produced much larger concentrations of Compound A (35.4 ppm and 34.2 ppm, respectively) at 2 h after exposure to sevoflurane. Medisorb(TM) showed measurable concentrations of Compound A (8.6 ppm at 2 h), but they were significantly smaller than those produced by the two conventional absorbents. In contrast, when Amsorb(TM) was used, Compound A concentrations remained at baseline throughout the study period. IMPLICATIONS: Carbon dioxide absorbents containing potassium hydroxide/sodium hydroxide produce much larger concentrations of Compound A from sevoflurane in clinical practice. An absorbent containing neither potassium hydroxide nor sodium hydroxide produces the smallest concentrations of Compound A.

Absorption↗

A biopsychosocial approach to finding common ground in the clinical encounter.

PURPOSE: Little is known about how clinicians find common ground in conflicts with their patients or how educators can teach physicians-in-training to do so. The authors set out to create a conceptual model for the process of finding common ground. METHOD: Students in a third-year family practice clerkship wrote up cases they had encountered in which conflicts arose in the patient-doctor relationship. The authors analyzed these cases, first independently and then collectively. After several iterations, they arrived at a model grounded in the case material. RESULTS: The authors suggest that a modification of the biopsychosocial model first proposed by Engel and later updated by McWhinney is an appropriate and practical schema for classifying sources of conflict. This hierarchical system consists of five levels: (1) individual patient, (2) relationship between patient and physician, (3) patient's family, (4) ethnic belief systems of patient and family, and (5) political economy. CONCLUSION: This hierarchical, multilevel biopsychosocial approach allows the clinician to identify the level in the system at which a conflict has arisen. This clarifies the strategies for resolution, making it easier for patient and doctor to find common ground. This may also be a useful heuristic model for teaching such skills to physicians-in-training.

Aged↗

Adult tethered cord syndrome.

Although often overlooked, the diagnosis of adult "tethered cord syndrome" (TCS) is important because the manifestations of this syndrome are readily reversible by untethering. Too often, adult patients with TCS are misdiagnosed as having "failed back syndrome" or other unrelated spinal problems. As a result, many patients are treated with modalities which fail to improve neurological function. The aims of this review are to acquaint readers with the pathophysiology, symptomatology, diagnosis, and treatment of adult TCS based on author's experience in 70 cases. Adult TCS manifested by severe back and leg pain, a subtle onset of motor/sensory changes and musculoskeletal deformities is correlated to TCS pathophysiology and imaging studies. Timely diagnosis of TCS can lead to pain relief and restoration of neurologic function and patient gratification.

Adult↗

Inhibitory effects of halothane, isoflurane, sevoflurane, and pentobarbital on the constriction induced by hypocapnia and bicarbonate in isolated canine cerebral arteries.

The effects of halothane, isoflurane, sevoflurane (0.5, 1 and 2 MAC) and pentobarbital (10(-5) M, 10(-4) M and 3 x 10(-4) M) on hypocapnia- and bicarbonate-induced constriction of isolated dog middle cerebral arteries were investigated in vitro. The isometric tension of isolated cerebral arterial rings was measured in an organ bath containing Krebs bicarbonate solution, aerated with 5% CO2 and 95% O2. Hypocapnia, induced by replacing the bathing solution with one that had been equilibrated with 2.5% CO2 and 97.5% O2, produced a sustained vasoconstriction (268 +/- 36 mg, mean +/- SEM). Exposure of arterial rings to a bathing solution that contained double the concentration of NaHCO3 (50 mM) elicited a phasic constriction followed by a gradual decrease in tension (309 +/- 34 mg). Although halothane, isoflurane, and sevoflurane attenuated both hypocapnia- and bicarbonate-induced constrictions in a dose-dependent manner, the inhibition of these constrictions was greater in rings treated with halothane than in those treated with isoflurane or sevoflurane when compared at equipotent concentrations. These alkaline-induced constrictions were attenuated by pentobarbital only at the highest concentration of 3 x 10(-4) M. Halothane (1 and 2 MAC) attenuated the constriction induced by hypocapnia to a greater extent than that induced by 15 mM KCl, whereas pentobarbital (10(-4) M and 3 x 10(-4) M) attenuated hypocapnia-induced constriction less than KCl-induced constriction. These results indicate that alkaline-induced constriction is more vulnerable to halothane than other volatile anesthetics and pentobarbital. The mechanisms of the inhibitory effects of halothane and pentobarbital on alkaline-induced cerebral vasoconstriction seem to differ; the inhibitory effect of pentobarbital, but not of halothane may be, in part, ascribed to its inhibitory effect on the Ca++ influx.

Anesthetics, Inhalation↗

Structure of cytochrome c6 from the red alga Porphyra yezoensis at 1. 57 A resolution.

The crystal structure of cytochrome c(6) from the red alga Porphyra yezoensis has been determined at 1.57 A resolution. The crystal is tetragonal and belongs to space group P4(3)2(1)2, with unit-cell parameters a = b = 49.26 (3), c = 83.45 (4) A and one molecule per asymmetric unit. The structure was solved by the molecular-replacement method and refined with X-PLOR to an R factor of 19.9% and a free R factor of 25.4%. The overall structure of cytochrome c(6) follows the topology of class I c-type cytochromes in which the heme prosthetic group covalently binds to Cys14 and Cys17, and the iron has an octahedral coordination with His18 and Met58 as the axial ligands. The sequence and the structure of the eukaryotic red algal cytochrome c(6) are very similar to those of a prokaryotic cyanobacterial cytochrome c(6) rather than those of eukaryotic green algal c(6) cytochromes.

Amino Acid Sequence↗

Correlation between deposition of immuno-components and infiltration pattern of polymorphonuclear leukocytes in the lesions of chronic urticaria.

Urticaria is often associated with perivascular infiltration of leukocytes into the lesions. Although mast cell-derived chemical mediators are considered to play crucial roles in the infiltration of leukocytes as well as in the dermal edema, other mechanisms for the leukocyte infiltration have not been well defined. This study revealed that approximately 25% of the cases of chronic idiopathic urticaria in whom wheals had continued for more than 12 h had deposition of immuno-components in the lesions, although histological examination of the lesions did not show leukocytoclastic vasculitis. In these lesions with deposition of immuno-components, both neutrophils and eosinophils had infiltrated at a constant ratio (approximately 2:1), whereas, in the lesions without deposition, a variable population of leukocytes was seen. This result suggests that activation of complements occurs in the lesions of a considerable percentage of patients with chronic idiopathic urticaria and that the complement fragments influence the infiltration patterns of polymorphonuclear leukocytes.

Adult↗

Ultrasonographic evaluation of lansoprazole-induced improvement of submucosal injury in patients with gastroesophageal reflux.

OBJECTIVE: Endoscopic ultrasonographic (EUS) changes in gastroesophageal reflux disease (GERD) after treatment with proton pump inhibitor have been poorly evaluated. We conducted a randomized, double-blind 12-wk clinical trial to compare the EUS effects of lansoprazole to histamine H2-receptor antagonist therapy in GERD. METHODS: Seventeen patients with reflux-related symptoms received 40 mg of famotidine for 6 wk or 30 mg of lansoprazole for 6 wk followed by 40 mg of famotidine or 30 mg of lansoprazole for another 6 wk, respectively. Patients underwent EUS before and at 6 and 12 wk after treatment. RESULTS: Before treatment, a variable degree of wall thickening was noted on EUS in the lower esophagus, compared with 20 normal subjects. After 6 wk of therapy, esophageal wall was significantly thicker in the famotidine group compared with the lansoprazole group (p<0.01). Surprisingly, thickening of esophageal wall and abnormal architecture were also detected in endoscopically negative reflux disease. Lansoprazole was superior to famotidine in reducing the thickness of esophageal wall. CONCLUSIONS: EUS was very useful for evaluation of submucosal injury in patients with GERD. EUS showed that a 6-wk course of lansoprazole therapy reduced thickening of esophageal wall, which was resistant to histamine H2-receptor antagonist therapy. Our results also suggest that inflammatory damage to the submucosal and muscle layers of the lower esophagus is the underlying mechanism of heartburn and associated symptoms in patients with endoscopically negative reflux disease.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Successful treatment of cap polyposis by avoidance of intraluminal trauma: clues to pathogenesis.

"Cap polyposis" is a rarely-encountered condition in which distinctive inflammatory polyps are located from the rectum to the distal descending colon. Microscopically, the polyps consist of elongated, tortuous, and distended crypts covered by a "cap" of inflammatory granulation tissue. Although the pathogenesis is unknown, mucosal prolapse has been postulated to be an important etiological factor, given certain clinical and histological similarities. We describe two cases of cap polyposis with protein-losing enteropathy. One was treated successfully by avoidance of straining at defecation. Another resolved after double-barreled transverse colostomy. Both successful treatments support a causal link of polyposis to prolapse.

Adult↗

Reconstitution of humoral immunity during pregnancy.

BACKGROUND: Recently, increasing attention has been paid to hormonal regulations of the immune system. MATERIALS AND METHODS: In this study, cord sera and the corresponding maternal sera were obtained at delivery. Sera from pregnant women were obtained at early, middle, and late stages of pregnancy. These sera were tested for titer and avidity of measles or mumps virus-specific immunoglobulin G (IgG) by means of a single-dilution, urea-denaturation enzyme-linked immunosorbent assay method. RESULTS: A positive and significant correlation was found between the titer and avidity of the virus-specific IgG, both in the cord sera and in the maternal sera. This correlation was established already at the early stage of pregnancy. There were no such correlations found in nonpregnant individuals. CONCLUSIONS: This is the first observation in human subjects that the avidity and concentration of the virus-specific IgG had a positive and significant correlation. Pregnancy must have some significant effects on the regulation of humoral immunity.

Adolescent↗

[Increasing nalidixic-acid-resistance in Salmonella strains isolated from sporadic cases in Tokyo].

A total of 118 nalidixic-acid (NA)-resistant Salmonella strains consisting of 68 domestic strains and 50 imported strains isolated during 1988-1998 in Tokyo were examined regarding their annual incidence, serovars, drug-resistance patterns, and minimum inhibitory concentrations(MIC) to fluoroquinolones (NFLX, OFLX, ENX, and CPFX). NA-resistant strains accounted for 1.3% of all Salmonella (5,302 strains) isolated from domestic cases, and 2.5% of all Salmonella (1,981 strains) isolated from imported cases. The incidence of NA-resistant strains has increased since 1995, and it has been remarkable in imported cases. The results of the serotyping showed that the NA-resistant strains were classified into 25 serovars, excluding untypable strains. Among those, S. Enteritidis (21 strains), S. Blockley (13 strains), S. Litchifield (13 strains), S. Typhimurium (13 strains), S. Hadar (9 strains), and S. Virchow (8 strains) were predominant. Drug-resistance patterns of NA-resistant strains, including other drugs (CP, TC, SM, KM, ABPC, ST, FOM, and NFLX) tested varied among the 26 types. Among those, multidrug-resistant strains accounted for 61.9% (73 strains), and one strain among them was high-resistant to NFLX. MIC distribution of NA-resistant strains to fluoroquinolones showed that the ranges of all drugs were 4-128 times higher than NA-sensitive strains used for controls.

Anti-Infective Agents↗

[Species and serovar-distribution, and drug-resistance of Shigella strains isolated from imported and domestic cases during 1995-1999 in Tokyo].

A total of 290 Shigella strains consisting of 180 imported strains and 110 domestic strains isolated during 1995-1999 in Tokyo were examined regarding their species and serovar-distribution and their drug-resistance. In both groups, S. sonnei (70.0% in the imported strains, 80.9% in the domestic strains) was found to be the most prevalent species, followed by S. flexneri (20.0% in the imported strains, 19.1% in the domestic strains). S. dysenteriae and S. boydii were only isolated in the imported cases. Among the S. flexneri serovar, 1b, 2a, 6, 2b, and 3a were predominant in the imported strains, whereas 1b and 2a were predominant in the domestic strains. Provisional new serovar Shigella strains were isolated from 11 imported cases and 2 domestic cases. The drug-resistance test using 9 drugs (CP, TC, SM, KM, ABPC, ST, NA, FOM, and NFLX) showed that 92.2% of the imported strains and 94.5% of the domestic strains were resistant to some of the drugs tested. Drug-resistance patterns of the resistant strains varied in 25 types. Among those, a triple drug-resistance type with TC.SM.ST was found as the most frequent pattern in both groups. None of the strains were resistant to NFLX.

Anti-Bacterial Agents↗

[Influenza virus surveillance in Tama, Tokyo--viral examinations in 1996/97, 1997/98, 1998/99, and 1999/2000 seasons].

During the 1996/97, 1997/98, 1998/99, and 1999/2000 seasons, isolations of influenza virus and/or confirmations of hemagglutinin gene of virus from the throat swab of patients in 9 medical institutions in Tama, Tokyo were carried out by RT-PCR and tissue culture with MDCK cells. In 1996/97 and 1997/98 seasons, type A (H3N2) was the predominant type of influenza virus, which was 85% in the 1996/97 and 97% in the 1997/98, but small-scale outbreaks with type B virus was also confirmed in the 1996/97 season (during the 8th and 10th week). On the other hand, in the other two seasons, 2 different kinds of types of virus were discovered, which was type A (H3N2) and type B in 1998/99 season, and H3N2 and H1N1 of type A virus in 1999/2000 season. In the 1998/99 season, type A (H3N2) prevailed in the first half, and type B gradually replaced type A (H3N2) after the 5th week in 1999, whereas 2 different kinds of type A in the 1999/2000 mixed during the outbreak. From the presented data, the difference of mode by age groups and year could be explained. Namely, most specimens and positive cases in 1996/97 and 1997/98 seasons were those from low age groups (fifteen years of age and below). In 1998/99 and 1999/2000 seasons, the number of specimens from high age groups (sixteen years of age or over) accounted for above 50%, and about 70% of type A (H3N2)-positive cases. Contrary, the frequency of type B virus in 1998/99 season and type A (H1N1) in 1999/2000 season was higher in the low age groups than the high ones.

Hemagglutination, Viral↗