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Biomedical subjects

T Gerhardt

Publications and source records attributed to T Gerhardt.

At least 19 recordsLinked to original sources

Cystatin C-based calculation of glomerular filtration rate in kidney transplant recipients.

Cystatin C (Cys C) has been shown to be an alternative marker of renal function. However, estimation of the glomerular filtration rate (GFR) based on Cys C has received little attention. Recently, several Cys C-based equations were developed in different patient cohorts. To date, the benefit of a Cys C-based GFR calculation in patients after renal transplantation (RTx) remains to be elucidated. We compared the diagnostic accuracy of three Cys C-based formulae (Larsson, Hoek, Filler which used an immunonephelometric method) with the results of the Modification of Diet in Renal Disease (MDRD) formula. GFR was measured by means of technetium-diethylenetriamine pentaacetic acid ((99m)Tc-DTPA) clearance in 108 consecutive patients after RTx. Correlation coefficients of all calculated GFR estimates with the true GFR were high but did not differ significantly from one another (0.83-0.87). The MDRD and Filler equations overestimated GFR significantly, whereas the Larsson equation significantly underestimated GFR. Bias of the Hoek formula was negligible. Precision of the Hoek (8.9 ml/min/1.73 m(2)) and Larsson equations (9.6 ml/min/1.73 m(2)) were significantly better than MDRD equations (11.4 ml/min/1.73 m(2); P< or =0.035 each). Accuracy within 30% of real GFR was 67.0 and 65.1% for the MDRD and Filler formulae, and 77.1% for the Larsson and Hoek formulae, respectively. Accuracy within 50% of true GFR for the Hoek formula (97.2%) was better than for the MDRD equations (85.3%). Cys C-based formulae may provide a better diagnostic performance than creatinine-based equations in GFR calculation after RTx.

Cystatin C↗

Detection of human aspartyl (asparaginyl) beta-hydroxylase and homeobox B7 mRNA in brush cytology specimens from patients with bile duct cancer.

BACKGROUND AND STUDY AIMS: The diagnosis of bile duct cancer is hampered by the low sensitivity of intraductal brush cytology and forceps biopsy. In the present study real-time reverse transcription polymerase chain reaction (RT-PCR) assays for the detection of human aspartyl (asparaginyl) beta-hydroxylase (HAAH) and homeobox B7 (HoxB7) mRNA from intraductal brush cytology specimens were established. Both markers are overexpressed in biliary cancer cell lines and possibly involved in the pathogenesis of bile duct cancer. PATIENTS AND METHODS: RT-PCR assays were validated for detection limit, in-assay variability, and inter-assay variability. Target gene expression was determined in brush cytology specimens from 16 patients with biliary strictures (11 with histologically proven cholangiocarcinomas and five with benign biliary strictures). RESULTS: The assay was quick (about 3 h), highly sensitive (with detection limits between 3 and 106 molecules), and reproducible (maximum in-assay variability 10.3 %, maximum inter-assay variability 11.8 %). The sensitivity of routine brush cytology alone was 36 % (four of 11 cases), with 100 % specificity. A combination with detection of HoxB7 and HAAH mRNA increased the overall diagnostic sensitivity to 82 %. CONCLUSIONS: Detection of these markers using the RT-PCR assays from brush cytology specimens described here may prove to be a useful additional tool for the diagnosis of bile duct carcinoma.

Adult↗

Calculation of glomerular filtration rate based on cystatin C in cirrhotic patients.

BACKGROUND: Plasma creatinine and creatinine clearance are of limited value for the estimation of renal function in cirrhotics. In these patients, cystatin C (Cys C) has been proposed as an alternative marker of glomerular filtration rate (GFR) and Cys C-based equations for calculation of GFR have been developed in non-cirrhotic patient cohorts. METHODS: We retrospectively analyzed correlation, bias, precision and accuracy of two Cys C-based formulae (Larsson and Hoek) for GFR estimation in comparison with two creatinine-based equations (Cockroft & Gault and MDRD). The Cys C was determined by an immunonephelometric method. The GFR was measured by means of inulin clearance in 44 consecutive patients with liver cirrhosis. RESULTS: On average, inulin clearance was 28.3 (95% CI: 29.2-41.3 ml/min/1.73 m2). Creatinine as well as Cys C-based equations overestimated the true GFR by 105-154%. However, Cys C-based equations showed significantly lower bias and higher precision than the creatinine-based formulae. Correlation and accuracy tended to be better with the Hoek and Larsson equation than with the Cockroft & Gault or MDRD formulae. Hoek and Larsson equations showed a similar diagnostic performance in all statistical procedures. CONCLUSION: Our data suggest a significant improvement of GFR estimation in liver cirrhotics by means of the Cys C-based Hoek and Larsson formulae. However, all estimates remain a crude approximation of true GFR and thus cannot replace gold standard methods.

Creatinine↗

Intravenous treatment of hyperhomocysteinemia in patients on chronic hemodialysis--a pilot study.

BACKGROUND: Treatment of hyperhomocysteinemia in patients with end-stage renal disease (ESRD) can be performed with the oral application of vitamins. However, this therapy rarely normalizes total homocysteine (tHcy) levels. Frequently, a rebound is observed after the end of treatment. Currently, no data are available about intravenous combination therapy with folic acid, pyridoxine (B6), and cyanocobalamin (B12). METHODS: We conducted a prospective pilot study comprising 13 patients on chronic hemodialysis treatment (63.7+/-4.9 years; 6 female, 7 male) for 27 weeks. The patients received 10 mg folic acid and 100 mg pyridoxine intravenously (IV) after each dialysis plus 1000 microg vitamin B12 IV once a week for 9 weeks. Between weeks 10 and 18 the patients received 10 mg folic acid, 100 mg vitamin B6 once a week, and 1000 microg vitamin B12 bimonthly IV. RESULTS: The therapy regimen decreased tHcy concentration (baseline: 30.5+/-2.2 micromol/L) significantly to 17.4+/-1.2 micromol/L, 15.6+/-1.0 micromol/L, and 16.4+/-0.1 micromol/L after 3, 6, and 9 weeks, respectively (p<0.01 vs. baseline concentration). The maximum reduction (-47.5+/-3.3%) of tHcy concentration was measured after 6 weeks of therapy. During the following maintenance therapy, tHcy-levels did not increase and no rebound of tHcy was detected during follow-up (week 27:16.5+/-1.97 micromol/L). CONCLUSION: The concept of a short, high-dose induction therapy with intravenous folic acid, pyridoxine, cyanocobalamin, and a subsequent low-dose maintenance regimen is effective in the treatment of hyperhomocysteinemia in patients with ESRD.

Aged↗

Cystatin C as an endogenous marker of glomerular filtration rate in renal transplant patients.

BACKGROUND: Serum creatinine is the most common endogenous marker used to estimate the glomerular filtration rate (GFR). However, creatinine depends considerably on muscle mass, and its tubular secretion increases, especially in chronic renal failure. Cystatin C is a 13-kD protease inhibitor which is produced by all nucleated cells and is independent of muscle mass and sex. Cystatin C is eliminated by glomerular filtration and metabolized by proximal tubular cells. Its measurement has been proposed as an alternative and more sensitive marker of GFR than creatinine in patients with slight to moderately decreased GFR. METHODS: We investigated serum cystatin C levels in comparison with creatinine as a single measurement for estimation of GFR in 173 patients after renal transplantation. GFR was calculated as creatinine clearance according to standard equations. RESULTS: Serum creatinine correlated well with cystatin C (r = 0.84; p < 0.0001). No significant differences were obtained for the comparison of the linear correlation of 1/creatinine with creatinine clearance (r = 0.77; p < 0.0001) and for the linear correlation of 1/cystatin C with creatinine clearance (r = 0.73; p < 0.0001). However, we found a significant advantage of cystatin C in detecting a clinical relevant reduction of kidney function (GFR <70 ml/min; p = 0.0047, McNemar test). CONCLUSION: Cystatin C is an alternative marker for the assessment of GFR in renal allograft recipients that may be superior to creatinine.

Adult↗

Preparation of severely curved simulated root canals using engine-driven rotary and conventional hand instruments.

This in vitro study evaluated the efficacy and safety of six different nickel-titanium engine-driven instruments used with a torque-controlled engine device and nickel-titanium hand and stainless steel hand instruments in preparation of curved canals. A total of 80 curved (36 degrees) simulated root canals were prepared. Images before and after were superimposed, and instrumentation areas were observed. Time of instrumentation, instrument failure, change in working length and weight loss were also recorded. Results show that stainless steel hand instruments cause significantly less transportation towards the inner wall of the canal than do nickel-titanium hand instruments. No instrument fracture occurred with hand instruments, but 30-60% breakage of instruments was recorded during instrumentation with the engine-driven devices. The working length was maintained by all types of instruments. Newly developed nickel-titanium rotary files were not able to prevent straightening of the severely curved canals when a torque-controlled engine-driven device was used.

Dental Alloys↗

Inductance plethysmography: an alternative signal to servocontrol the airway pressure during proportional assist ventilation in small animals.

During proportional assist ventilation (PAV), the ventilator pressure is servocontrolled throughout each spontaneous inspiration such that it instantaneously increases in proportion to the airflow (resistive unloading mode), or inspired volume (elastic unloading mode), or both (combined unloading mode). The PAV pressure changes are generated in a closed-loop feedback circuitry commonly using a pneumotachographic signal. In neonates, however, a pneumotachograph increases dead space ventilation, and its signal may include a substantial endotracheal tube leak component. We hypothesized that respiratory inductive plethysmography (RIP) can replace pneumotachography to drive the ventilator during PAV without untoward effects on ventilation or respiratory gas exchange. Ten piglets and five rabbits were supported for 10-min (normal lungs) or 20-min (meconium injured lungs) periods by each of the three PAV modes. In each mode, three test periods were applied in random order with the ventilator driven by the pneumotachograph signal, or the RIP abdominal band signal, or the RIP sum signal of rib cage and abdomen. Interchanging the three input signals did not affect the regularity of spontaneous breathing, and gas exchange was achieved with similar peak and mean airway pressures (ANOVA). However, the RIP sum signal worked adequately only when the relative gains of rib cage and abdominal band signal were calibrated. We conclude that an RIP abdominal band signal can be used to generate PAV, avoiding increased dead space and endotracheal tube leak problems.

Airway Resistance↗

Proportional assist ventilation decreases thoracoabdominal asynchrony and chest wall distortion in preterm infants.

Thoracoabdominal asynchrony (TAA) and chest wall distortion (CWD) are commonly seen in preterm infants secondary to a highly compliant rib cage and poor compensation of distorting forces by inspiratory rib cage muscles. Continuous positive airway pressure (CPAP) reduces TAA and CWD by stenting the chest wall. We hypothesized that application of positive airway pressure only during inspiration and in proportion to an infant's inspiratory effort should have a similar but more pronounced effect than CPAP alone. A ventilator providing airway pressure changes in proportion to flow and volume generated by an infant (proportional assist ventilation) was used to unload the respiratory pump during inspiration. Ten preterm infants were studied [birth weight, 745 (635-1175) g; gestational age, 26.5 (24-31) wk; postnatal age 3 (1-7) d; medium (range)]. TAA and CWD were determined by respiratory inductive plethysmography. TAA was expressed as the phase angle between the rib cage and abdominal motion and CWD as the total compartmental displacement ratio. In addition, we measured tidal volume with a pneumotachograph and esophageal and airway pressure deflections with pressure transducers. Measurements were obtained during alternating periods of CPAP and two different degrees of support (Gain 1 = 1.09 +/- 0.68, Gain 2 = 1.84 +/- 0.84 cm H(2)O/mL) that were provided by a proportional assist ventilator. Phase angle and the total compartmental displacement ratio decreased with increasing gain compared with CPAP alone. Peak airway pressure increased from 0.6 to 3.8 to 7.6 cm H(2)O above positive end-expiratory pressure (PEEP) with CPAP, Gain 1, and Gain 2, respectively, as tidal volume increased from 2.8 to 4.1 to 4.7 mL/kg. Esophageal pressure changes decreased only little with increasing gain. Chest wall excursion increased and abdominal movement decreased, indicating a redistribution of tidal volume between chest and abdomen. We conclude that proportional assist ventilation reduces TAA and CWD by generating a small increase in airway pressure that occurs in synchrony and in proportion to each inspiratory effort.

Abdomen↗

Closed-loop controlled inspired oxygen concentration for mechanically ventilated very low birth weight infants with frequent episodes of hypoxemia.

BACKGROUND: Mechanically ventilated very low birth weight infants often present with frequent episodes of hypoxemia, and maintaining arterial oxygen saturation by pulse oximetry (SpO(2)) within a normal range by manual fraction of inspired oxygen (FIO(2)) adjustments is difficult and time consuming. OBJECTIVES: An algorithm for closed-loop FIO(2) control (cFIO(2)) to maintain SpO(2) within a target range was compared with continuous manual FIO(2) (mFIO(2)) adjustments by a nurse in a group of ventilated infants who presented with frequent episodes of hypoxemia. RESULTS: Fourteen infants (birth weight: 712 +/- 142 g; gestational age: 25 +/- 1.6 weeks; age: 26 +/- 11 days; synchronized intermittent mandatory ventilation rate: 24 +/- 10 b/m; peak inspiratory pressure: 17.5 +/- 2.0 cmH(2)O; positive end-expiratory pressure: 4.3 +/- 0.5 cmH(2)O) were studied for 2 hours on each mode in random sequence. Both modes aimed to maintain SpO(2) between 88% and 96%. There were 15 +/- 7 and 16 +/- 6 hypoxemic episodes/hour (SpO(2) <88%, >5 s) during mFIO(2) and cFIO(2), respectively; episode duration was 41 +/- 23 and 32 +/- 15 s, totaling 19 +/- 16% and 17 +/- 12% of recording time. There were 13 +/- 10 and 10 +/- 8 hyperoxemic episodes/hour (SpO(2)>96%, >5 s) during mFIO(2) and cFIO(2,) respectively; episode duration was 27 +/- 15 and 24 +/- 19 s, totaling 15 +/- 14% and 10 +/- 9% of recording time. Mean SpO(2) and FIO(2) levels were similar during both modes. The nurse made 29 +/- 17 adjustments/hour during mFIO(2). There was a significant increase in the duration of normoxemia (SpO(2) between 88%-96%) during cFIO(2) (75 +/- 13 vs 66 +/- 14% of recording time). CONCLUSION: In this group of infants, cFIO(2) was at least as effective as a fully dedicated nurse in maintaining SpO(2) within the target range, and it may be more effective than a nurse working under routine conditions. We speculate that during long-term use, cFIO(2) may save nursing time and reduce the risks of morbidity associated with supplemental oxygen and episodes of hypo- and hyperoxemia.

Algorithms↗

Comparative study of composite resin placement: centripetal buildup versus incremental technique.

An in vitro study was performed to evaluate the effect of two different proximal restoration techniques with different matrix systems on the marginal seal and microhardness of Class II composite restorations. Results indicated that the lowest, however, not significantly different, microleakage was achieved in totally bonded deep Class II restorations prepared with margins surrounded by enamel when using transparent matrices and reflective wedges in combination with the centripetal buildup technique. Highest surface hardness of composite resin was related to transparent matrices and reflecting wedges.

Coloring Agents↗

In vitro dentinal surface reaction of 9.5% buffered hydrofluoric acid in repair of ceramic restorations: a scanning electron microscopic investigation.

STATEMENT OF PROBLEM: Fracture of porcelain is a relatively common clinical misfortune. Recent research has indicated that strong bonds can be formed between composite and dental porcelain. Porcelain surfaces are etched with hydrofluoric acid and treated with silane coupling agents before composite application. The question is how exposed dentin may react to etching with hydrofluoric acid. PURPOSE: This investigation examined the effect of 9.5% buffered hydrofluoric acid, of 36% o-phosphoric acid alone and in combination on the surface structure of cut human dentin. MATERIAL AND METHODS: Human molar teeth were sectioned in approximately 0.8-mm thick slices and treated with different acids or their combinations. Application periods were 10, 60, and 180 seconds. Specimens were processed for SEM and for energy-dispersive x-ray (EDX) microanalysis. RESULTS: The smear layer on the surface of sectioned dentin was not completely removed by hydrofluoric acid alone and that a dense amorphous precipitate was formed on the peritubular zone. Starlike structures in dentinal tubules were visible. EDX analysis revealed different fluoride content on the treated surface, dependent on the etchant used. CONCLUSION: Topical application of hydrofluoric acid appeared to provide a dentinal surface with an amorphous precipitate of fluoride. This layer may be important both for resistance of dental caries in dentin and for bonding reactions.

Acid Etching, Dental↗

Proportional assist ventilation in low birth weight infants with acute respiratory disease: A comparison to assist/control and conventional mechanical ventilation.

OBJECTIVES: To compare the physiologic efficacy and safety aspects of proportional assist (PA), assist/control (A/C), and intermittent mandatory ventilation (IMV) in very low birth weight infants with acute respiratory illness and to test the hypothesis that ventilatory pressure requirements are lower and arterial oxygenation is improved during PA when compared with IMV or A/C at an equivalent inspired oxygen fraction. STUDY DESIGN: Randomized, 3-period, crossover design. METHODS: Thirty-six infants were stratified by birth weight (600 to 750, 751 to 900, and 901 to 1200 g) and exposed to consecutive 45-minute epochs of the 3 modalities in a sequence chosen at random. Tidal volumes of 4 to 6 mL/kg were targeted during A/C and IMV. The IMV rate was matched to the rate during an A/C test period. PA was adjusted to unload the resistance of the endotracheal tube and the disease-related increase in lung elastic recoil. RESULTS: Compared with A/C and IMV, PA maintained similar arterial oxygenation with lower airway and transpulmonary pressures (15% to 44% reduction depending on the index variable). The oxygenation index decreased by 28% during PA. No adverse events were observed. The number and severity of apneic episodes and periods of arterial oxygen desaturations were similar with the 3 modes. Similar results were obtained within each birth weight subgroup. CONCLUSIONS: PA safely maintains gas exchange with smaller transpulmonary pressure changes compared with A/C and IMV. It may therefore offer a way of reducing the incidence of chronic lung disease in low birth weight infants.

Acute Disease↗

A new method to analyze lung compliance when pressure-volume relationship is nonlinear.

Changes in dynamic lung compliance during inspiration and expiration cannot be modeled accurately with conventional algorithms. We developed a simple method to analyze pressure-volume (P/V) relationships under condition of nonlinearity (APVNL) and tested it in a lung model with known resistance and nonlinear P/V relationship. In addition, pulmonary mechanics in 22 infants, 11 of them with nonlinear P/V relationships, were analyzed with the new method. The findings were compared with those obtained by a recently introduced algorithm, multiple linear regression analysis (MLR) of the equation of motion. The APVNL method described the changing compliance (C) of the lung model accurately, whereas the MLR method underestimated C especially in the first half of the breath. In infants the MLR method gave highly variable, often nonphysiological C values in the beginning of a breath. In contrast, the coefficient of variability of measurements obtained by the APVNL method was significantly smaller (p < 0.02), and the indices of model-fit showed better agreement between calculated and observed pressure than for the MLR method (p < 0.02). We conclude that the APVNL method accurately describes nonlinear P/V relationships present during spontaneous breathing or mechanical ventilation. The method may be helpful in identifying and preventing pulmonary overdistention.

Airway Resistance↗

Effects of respiratory mechanical unloading on thoracoabdominal motion in meconium-injured piglets and rabbits.

Impaired pulmonary mechanics can cause chest wall distortion (CWD) so that work of breathing is dissipated in deforming the rib cage. We hypothesized that respiratory mechanical unloading as a technique of assisted mechanical ventilation would reduce CWD in animals with injured lungs. We studied five piglets and five adult rabbits to test across different ages and chest configurations. As a result of intratracheal meconium instillation, lung compliance decreased from 21 (median; range 17-35) to 9.5 (6.7-14) mL/kPa/kg in rabbits and from 26 (18-31) to 7.9 (4.9-11) in piglets. Airway resistance increased from 5.0 (4.6-6.1) to 6.9 (5.8-7.9) kPa/L/s in rabbits only. Respiratory inductive plethysmography was used to measure the phase shift between the rib cage and abdominal compartment movements and the total compartmental displacement ratio. We aimed at unloading at least three-fourths of lung elastance in all animals and 2.0 kPa/L/s of resistance in rabbits. Elastic unloading decreased the phase shift in all but one animal. It reduced the total compartmental displacement ratio from 1.27 (1.14-3.73) to 1.16 (1.02-1.82) in piglets and from 1.77 (1.45-5.24) to 1.37 (1.11-4.78) in rabbits. The inspiratory rib cage expansion increased, whereas abdominal expansion did not. The tidal esophageal pressure deflection decreased. Tidal volume increased, whereas respiratory rate remained unaffected so that the partial pressure of arterial CO2 decreased. Resistive unloading as an adjunct to elastic unloading further reduced CWD and induced a more rapid, shallower breathing. We conclude that respiratory unloading as a mechanical support to spontaneous breathing reduces CWD. We speculate that the decrease in CWD increases ventilatory efficiency for a given diaphragmatic effort.

Abdomen↗

Increased incidence of sighs (augmented inspiratory efforts) during synchronized intermittent mandatory ventilation (SIMV) in preterm neonates.

A reflex resulting in a deep, sigh-like inspiratory effort (augmented breath) is frequently triggered during synchronized mechanical ventilation in preterm infants. We studied the incidence of augmented inspiratory efforts and their effect on ventilation and lung compliance during conventional IMV and synchronized IMV (SIMV) in 15 preterm neonates (GA 26.7 +/- 1.5 wks (mean +/- SD), BW 925 +/- 222 g, age 1-8 days). Augmentation of spontaneous inspiratory effort was defined as an esophageal pressure deflection occurring coincident with a synchronized mechanical breath and exceeding the previous unassisted spontaneous effort by more than 50%. The incidence of augmented breaths was higher during SIMV (11.1 +/- 7.7%; P < 0.01) than during conventional IMV (5.1 +/- 6.1%). However, when the synchronized breaths were triggered late (200-300 msec) after the onset of inspiration, augmented breaths occurred no more frequently than during conventional IMV (6.0 +/- 4.7%). The incidence of augmented breaths correlated inversely with dynamic lung compliance (P = 0.014), but was not significantly influenced by a change in PEEP. Although inspiratory effort increased nearly three times during the augmented breaths, tidal volume increased only 12%. The change in tidal volume was limited because the augmented effort reached its maximal negativity only approximately 500 ms after the beginning of the synchronized, mechanical breath and at a time when the mechanical breath had already ended. For this reason the augmented effort did not contribute significantly to minute ventilation, but only prolonged inspiration. Dynamic lung compliance did not change significantly after an augmented breath. The results indicate that augmented inspiratory efforts are more common in preterm neonates ventilated with SIMV than with conventional IMV, but do not contribute significantly to ventilation.

Cohort Studies↗

Computer-controlled minute ventilation in preterm infants undergoing mechanical ventilation.

INTRODUCTION: Computer-controlled minute ventilation (CCMV) continuously adjusts the ventilator rate to changes in spontaneous respiratory drive and pulmonary mechanics to maintain a preset total minute ventilation. HYPOTHESIS: We hypothesized that CCMV would maintain ventilation and oxygenation with fewer mechanical breaths than conventional intermittent mandatory ventilation in very low birth weight infants. METHODS: Very low birth weight infants in clinically stable condition who were undergoing mechanical ventilation were enrolled. The number of mechanical breaths, total and mechanical expiratory minute ventilation, mean airway pressure, oxygen hemoglobin saturation by pulse oximetry, and transcutaneous partial carbon dioxide and partial oxygen tensions were obtained during intermittent mandatory ventilation and CCMV (45 to 60 minutes) and compared by paired t test. RESULTS: Fifteen infants were studied. Birth weight (median, range) was 700 gm (550 to 1205 gm), gestational age 26 weeks (23 to 34 weeks), age 21 days (3 to 50 days). When switched from intermittent mandatory ventilation to CCMV, the number of mechanical breaths was reduced (15 +/- 2.8 to 8.6 +/- 2.9 breaths per minute, p < 0.001), leading to lower airway pressure (3.97 +/- 1.00 to 3.45 +/- 1.00 cm H2O, p < 0.001) and lower expiratory minute ventilation generated by the mechanical ventilator (116 +/- 31 to 65 +/- 28 ml/min per kilogram, p < 0.001), while total expiratory minute ventilation remained unchanged. Mean transcutaneous partial carbon dioxide and oxygen tensions, oxygen hemoglobin saturation, and the time spent within different oxygen hemoglobin saturation ranges did not differ between both ventilatory modes. CONCLUSION: CCMV maintained adequate ventilation and oxygenation with lower mechanical ventilatory support than IMV. CCMV may reduce barotrauma and chronic lung disease during long-term use.

Down-Regulation↗