抗精浆免疫抑制物抗体的抗生育机理研究

作者进行了抗精浆免疫抑制物抗体（ＳＰＩＭ－Ａｂ）的补体结合功能测定（ＣＦＡ）和ＳＰＩＭ－Ａｂ对精子凝集、制动、穿透力和杀精子影响的研究。结果表明，ＳＰＩＭ－Ａｂ阳性不育病人（ｎ＝２９）ＣＦＡ值为６．４７±１．５５ｋＵ／Ｌ，明显低于ＳＰＩＭ－Ａｂ阴性病人（ｎ＝７ｌ，８．１１±１．６２ｋＵ／Ｌ）和对照组（ｎ＝３０，８．６０±１．８０ｋＵ／Ｌ），Ｐ＜０．０１。经ＳＰＩＭ－Ａｂ阳性血清和ＳＰＩＭ－Ａｂ阴性血清作用后，两组精子凝集、制动和死精子百分率分别为４１．４％和２１．１％、６９．０％和１６．９％、６２．１％和４．２％，精子穿透高度分别为３１．６±１３．０ｍｍ和３８．Ｏ±１２．９ｍｍ，经统计学处理差异显著（Ｐ＜０．０５～ｐ＜０．０１）。提示ＳＰＩＭ－Ａｂ能够以抗原抗体复合物形式激活补体，其对精子凝集、制动、杀伤和穿透力的影响，可能是干扰生育的重要原因之一。     

128对不育夫妇血清,精浆抗精浆免疫抑制物抗体与精液检查关系的分析

我们检测了８９对生育夫妇和１２８对不育夫妇血清、精浆中抗精浆免疫抑制物抗体（ＳＰＩＭ－Ａｂ）的水平。结果表明，不育夫妇血清、精浆ＳＰＩＭ－Ａｂ的水平和检出率均明显高于生育组（Ｐ＜０．０１）；精浆ＳＰＩＭ－Ａｂ水平增高者的精子密度、精子活率、精子运动速度和ＳＰＩＭ活性均明显降低（Ｐ＜０．０１）。提示：ＳＰＩＭ－Ａｂ水平增加可能影响生育。     

免疫印迹法分析抗SPIM抗体与临床应用

采用聚丙烯酰胺凝胶电泳和免疫印迹法分析不育症病人抗精浆免疫抑制物抗体（ＳＰＩＭ－Ａｂ）对特异抗原的免疫反应，并与ＥＬＩＳＡ法进行比较。结果表明，免疫印迹法检测血清、清浆ＳＰＩＭ－Ａｂ阳性率分别为３０．３％（３２／１０７）和２９．０％（３６／１２４），ＥＬＩＳＡ法检测分别为３３．６％（３６／１０７）和３１．５％（３９／１２４），Ｘ２＝１２９．５８，Ｐ＜０．０１．免疫印迹法分析的６８份不育症病人的血清、精浆ＳＰＩＭ－Ａｂ阳性样本中，４９份（７２．１％）与特异抗原的分子量１１００００和（或）９４０００区带发生免疫反应，１９份（２７．９％）与分子量５２０００区带反应，１３份（１９．１％）与分子量３６０００区带反应。提示大分子量ＳＰＩＭ抗原可能更容易诱导高效价ＳＰＩＭ－Ａｂ产生，并形成抗原抗体免疫复合物干扰生育。     

抗精浆免疫抑制物抗体对精子凝集和制动的影响

抗精浆免疫抑制物抗体对精子凝集和制动的影响陈金，黄邱朝，徐建平，黄宇烽精浆免疫抑制物（ＳＰＩＭ）能够抑制机体对精细胞的免疫反应，保护受精卵免遭排斥［１，２］。我们曾报道［３］，精浆抗ＳＰＩＭ抗体（ＳＰＩＭ－Ａｂ）水平增高者，ＳＰＩＭ活性降低，精子活率...     

128对不育夫妇血清、精浆抗精浆免疫抑制物抗体与精液检查关系的分析

我们检测了８９对生育夫妇和１２８对不育夫妇血清、精浆中抗精浆免疫抑制物抗体（ＳＰＩ—Ａｂ）的水平。结果表明，不育夫妇血清、精浆ＳＰＩＭ—Ａｂ的水平和检出率均明显高于生育组（Ｐ＜０．０１）；精浆ＳＰＩＭ—Ａｂ水平增高者的精子密度、精子活率、精子运动速度和ＳＰＩＭ活性均明显降低（Ｐ＜０．０１）。提示：ＳＰＩＭ—Ａｂ水平增加可能影响生育。     

免疫印迹法分析抗SPIM抗体与临床应用

采用聚丙烯酰胺凝胶电泳和免疫印迹法分析不育症病人抗精浆免疫抑制物抗体（ＳＰＩＭ－Ａｂ）对特异抗原的免疫反应，并与ＥＬＩＳＡ法进行比较，结果表明，免疫印迹法检测血清，精浆ＳＰＩＭ－Ａｂ阳性率分别为３０．３％（３２／１０７）和２９．０％（３６／１２４）ＥＬＩＳＡ法检测分别为３３．６％（３６／１０７）和３１．５％（３９／１２４），Ｘ＾２＝１２９．５８，Ｐ〈０．０１，免疫印迹法分析的６８从不育症病人的血清     

213例不育男性抗精子抗体与精液有关参数的分析

我们检测了９００多例男性不育症患者的血清、精浆抗精子抗体（ＡｓＡｂ）和精液各项指标，对其中２１３例ＡｓＡｂ阳性患者的精液有关参数与ＡｓＡｂ的关系进行了分析，并与生育男性组作了比较。结果表明，ＡｓＡｂ阳性患者的精子密度、精子活率、精子顶体完整率、精浆免疫抑制物（ＳＰＩＭ）及α－糖苷酶均明显低于生育组（Ｐ＜０．０１），不育男性ＡｓＡｂ阳性组ＳＰＩＭ阳性率也明显高于ＡｓＡｂ阴性组（Ｐ＜０．０１）。此外，血清与精浆ＡｓＡｂ同为阳性组的精子活率明显低于单纯血清或精浆ＡｓＡｂ阳性组（Ｐ＜０．０１）。     

胫骨定量超声测量及临床应用探讨

用ＳｏｕｎｄＳｃａｎ２０００骨定量超声（ＱＵＳ）仪测量胫骨超声速度（ＳＯＳ），同时与单光子吸收法（ＳＰＡ）测量前臂１／３处骨矿密度（ＢＭＤ）比较。两方法测得２０８例患者和健康志愿者结果相关（ｒ＝０．６７８，Ｐ＜０．００１）。４２例健康绝经妇女ＳＯＳ和ＢＭＤ与绝经时间呈负相关（ｒ＝－０．４１７和－０．４７９，Ｐ＜０．０１），７３例＞４０岁的健康志愿者ＳＯＳ和ＢＭＤ与年龄呈负相关（ｒ＝－０．２９３和－０．３７３，Ｐ＜０．０５）。与性别和年龄相匹配的正常参考值比较，结果＜ｘ－２ｓ者ＱＵＳ检出３４例，占１６．３％；ＳＰＡ２３例，占１１．０％，ＱＵＳ的诊断敏感度约是ＳＰＡ的１．５倍。     

胆汁酸代谢经典途径酶基因表达与豚鼠胆石病关系的研究

目的：研究豚鼠肝脏胆汁酸代谢经典途径关键酶──胆固醇７α一羟化酶（ＣＹＰ７ａｌ）和甾醇１２α－羟化酶（ＣＹＰ８ｂ１） 的基因表达与胆汁脂质含量及胆固醇结石形成的关系。方法：采用点杂交技术检测对照组（ｎ＝８）（普通豚鼠饲料喂 养）、未成石组（ｎ＝１３）和成石组豚鼠（ｎ＝９）（致石饲料喂养）肝脏ＣＹＰ７ａｌ和ＣＹＰ８ｂ１ ｍＲＮＡ的相对含量,并对三组豚 鼠胆汁脂质成份进行检测和分析。结果： １、与对照组豚鼠（ｎ＝８）相比,成石组豚鼠（ｎ＝８）肝脏ＣＹＰ７ａ１ ｍＲＮＡ的相对 含量显著减少（０．３９±０．１９比０．７３±０．３６,Ｐ＝０．０３）,ＣＹＰ７ａ１的ｍＲＮＡ相对量与胆汁胆固醇摩尔浓度、胆固醇在胆汁胆 固醇、胆汁酸和磷脂三者中的摩尔百分数、胆汁中胆汁酸摩尔浓度皆无明显相关。２、对照组（ｎ＝８）、未成石组（ｎ＝８）和 成石组豚鼠（ｎ＝８）肝脏ＣＹＰ８ｂ１ ｍＲＮＡ的相对含量无显著差异。３、未成石组（ｎ＝１３）和成石组豚鼠（ｎ＝９）胆汁胆固醇 浓度明显高于对照组（ｎ＝８）,分别为：０．５０ｍｍｏｌ／Ｌ±０．０９ｍｍｏｌ／Ｌ比０．３９ｍｍｏｌ／Ｌ±０．１１ｍｍｏｌ／Ｌ,Ｐ＝０．０３;０．５０ｍｍｏｌ／Ｌ ±０．１０ｍｍｏｌ/     

精浆酸性磷酸酶活性与抗精子抗体

目的：探讨男性不育症精浆酸性磷酸酶（ＡＣＰ）与精子密度、精子成活率、血清和精浆抗精子抗体（ＡｓＡｂ）之间的关系。方法：检测不育男性精子密度、精子活率、血清和精浆ＡｓＡｂ及精浆ＡＣＰ活性。结果：精子成活率＞５０％、３０％～５０％、＜３０％组的精浆ＡＣＰ活性逐渐降低,分别为（１６２．１２±８５．７７）Ｕ／ｍｌ、（１２３．０１±５２．５５）Ｕ／ｍｌ和（１１１．２１±５４．４２）Ｕ／ｍｌ;与成活率＞５０％的精浆ＡＣＰ相比,活率在３０％～５０％和＜３０％组的ＡＣＰ活性降低,具有显著性差异（ＳＮＫ检验,Ｐ＜０．０１）;精子密度＞２０×１０９／Ｌ、（１０～１９）×１０９／Ｌ和＜１０×１０９／Ｌ组的精浆ＡＣＰ活性依次下降,分别为（１６５．９９±８８．６７）Ｕ／ｍｌ、（１３９．１９±７０．７８）Ｕ／ｍｌ和（１１５．２１±６０．５１）Ｕ／ｍｌ;与密度＞２０×１０９／Ｌ组的ＡＣＰ活性相比,密度在（１０～１９）×１０９／Ｌ和＜１０×１０９／Ｌ的精浆ＡＣＰ活性降低,具有显著性差异（ＳＮＫ检验,Ｐ＜０．０１）;血清、精浆ＡｓＡｂ阳性病人的ＡＣＰ活性明显低于二者均阴性的病人,且ＡＣＰ降低具有显著性差异（ＳＮＫ检验,Ｐ＜０．０１）。结论：?     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.