卡马西平联合苯巴比妥对癫痫患者认知功能及不良反应的影响

目的探讨卡马西平联合苯巴比妥对癫痫患者认知功能及不良反应的影响。方法选择2016年11月～2018年11月本院收治的癫痫患者共78例,依随机数字表法分成观察组(39例)与对照组(39例)。对照组给予卡马西平治疗,观察组则在对照组基础上联合苯巴比妥治疗,将两组治疗总有效率、癫痫发作次数、不良反应状况与蒙特利尔认知评估量表(MoCA)评分进行比较。结果对照组的总有效率74.36%,观察组为92.31%,差异具有统计学意义(P<0.05);治疗期间,观察组癫痫发作次数[(3.60±0.22)次/月]低于对照组[(4.11±0.24)次/月],差异具有统计学意义(P<0.05);观察组的不良反应发生率为12.82%,略高于对照组的7.69%,差异无统计学意义(P>0.05);治疗结束时,观察组MoCA评分[(26.66±2.31)分]高于对照组[(21.80±2.24)分],差异具有统计学意义(P<0.05)。结论卡马西平联合苯巴比妥治疗癫痫的临床效果显著,能有效减少癫痫发作次数,提高患者认知功能,且安全性较高。     

卡马西平片联合苯巴比妥对癫痫患者Bcl-2、IL-1β及Bax表达的影响

目的：探讨卡马西平联合苯巴比妥对癫痫患者B淋巴细胞瘤-2基因、白细胞介素-1?茁及前凋亡蛋白表达的影响。方法：回顾性分析2017年1月~2019年12月于神经内科接受治疗的61例癫痫患者的临床资料,将采用卡马西平联合苯巴比妥治疗的患者纳入观察组（31例）,将采用卡马西平治疗的患者纳入对照组（30例）。比较两组临床疗效、认知功能、B淋巴细胞瘤-2基因表达、白细胞介素-1?茁表达、前凋亡蛋白表达以及治疗期间不良反应发生情况。结果：观察组临床总有效率高于对照组,差异有统计学意义（P＜0.05）。两组治疗8周后蒙特利尔认知评估量表评分、B淋巴细胞瘤-2基因水平均较治疗前上升,白细胞介素-1?茁、前凋亡蛋白水平下降,且观察组蒙特利尔认知评估量表评分、B淋巴细胞瘤-2基因水平更高,白细胞介素-1?茁、前凋亡蛋白水平更低,差异有统计学意义（P＜0.05）。两组不良反应发生率比较,差异无统计学意义（P＞0.05）。结论：癫痫患者采用卡马西平联合苯巴比妥治疗的效果良好,可提升患者认知功能,改善B淋巴细胞瘤-2基因、白细胞介素-1?茁及前凋亡蛋白表达水平,且安全性较高。     

硫酸镁辅助治疗难治性癫痫46例临床分析

目的 :探讨硫酸镁辅助治疗难治性癫痫的剂量、方法及疗效。方法 :治疗组 46例 ,常规抗癫痫药物治疗同时加用 16.5 %硫酸镁 10ml口服 ,对照组 2 3例给予常规抗癫痫药物 ,卡马西平或苯妥英钠加苯巴比妥或氯硝西泮加用γ -氨基丁酸等治疗。结果 :治疗组有效率 84.78% ,对照组有效率 43 .48%。两组比较经统计学分析 P <0 .0 1,差异极显著。结论 :硫酸镁联合一线抗癫痫药治疗方法简单易行 ,具有良好效果     

卡马西平、脑活素等联合治疗癫痫62例的疗效

卡马西平、脑活素等联合治疗癫痫６２例的疗效广东省清远市人民医院陈惠霞目前国内外治疗癫痫大部着重控制症状，对巩固疗效，提高智能及恢复生活、劳动能力不够满意。本文采用卡马西平、苯巴比妥钠加脑活素、维生素Ｂ６治疗６２例，收到满意效果。１资料及方法１．１临床...     

丙戊酸钠缓释片联合卡马西平治疗额叶癫痫的效果分析

目的:探讨采用丙戊酸钠缓释片联合卡马西平在额叶癫痫中的应用效果及安全性。方法:选取2014年5月~2015年5月我院收治的额叶癫痫患者80例,随机分为对照组和观察组各40例。对照组给予卡马西平治疗,观察组给予丙戊酸钠缓释片联合卡马西平治疗,比较两组患者治疗效果及不良反应发生情况。结果:观察组患者治疗总有效率显著高于对照组,不良反应发生率低于对照组(P0.05)。结论:丙戊酸钠缓释片联合卡马西平治疗额叶癫痫疗效显著,可明显减少不良反应发生,值得临床推广应用。     

卡马西平与左乙拉西坦对癫痫的疗效和对血脂、 骨代谢的影响比较

目的:研究卡马西平与左乙拉西坦对癫痫的疗效和对血脂、骨代谢的影响。方法:新确诊癫痫患者84例,随机分为卡马西平组和左乙拉西坦组,各42例,分别采用卡马西平与左乙拉西坦治疗。比较2组临床疗效,检测并比较2组治疗前后的甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平;血清碱性磷酸酶、血钙、血磷、甲状旁腺素及骨特异碱性磷酸酶等骨代谢指标。结果:卡马西平组的有效率为83.33%(35/42),左乙拉西坦组为88.09%(37/42),2组差异无统计学意义(P0.05);2组治疗后TG、TC、LDL-C水平均明显高于同组治疗前(P0.05),但2组间差异无统计学意义(P0.05);2组治疗前后血清碱性磷酸酶、血钙、血磷、甲状旁腺素及骨特异碱性磷酸酶等骨代谢指标差异无统计学意义(P0.05),且2组间差异无统计学意义(P0.05)。结论:卡马西平和左乙拉西坦对癫痫的疗效相当,治疗半年可引起血脂水平升高,但对骨代谢无明显影响。     

病毒性脑炎继发癫痫临床特征及抗癫痫药物干预效果研究

目的:探讨病毒性脑炎继发癫痫的临床特征及不同抗癫痫药的干预效果.方法:对115例病毒性脑炎继发癫痫患者的临床资料进行回顾性分析.结果:本组患者中以难治性癫痫居多(73.9％),其中难治性癫痫患者的年龄及癫痫病程均显著低于非难治性癫痫患者(P＜0.01);癫痫类型均以继发强直阵挛及复杂部分性、单纯部分性为主.抗癫痫治疗多为联合用药(90.4％),应用抗癫痫药物频率排前5位依次为左乙拉西坦、丙戊酸盐、卡马西平、氯硝西泮、苯巴比妥;有效率依次为左乙拉西坦87.5％、苯巴比妥75.0％、氯硝西泮73.3％、卡马西平71.4％、丙戊酸盐66.7％.结论:病毒性脑炎继发癫痫以难治性癫痫为主,多采取联合用药,其中新型抗癫痫药物左乙拉西坦疗效最佳,可单用也可联合,视患者实际情况确定.     

奥卡西平与左乙拉西坦治疗新诊癫痫的疗效

目的:观察奥卡西平与左乙拉西坦治疗新诊癫痫的疗效及对血脂、骨代谢的影响。方法:107例新诊的原发性癫痫患者随机分为奥卡西平组(52例)和左乙拉西坦组(55例),分别给予奥卡西平或左乙拉西坦单药治疗。治疗6月后观察2组疗效以及血脂指标、骨代谢指标变化情况。结果:2组疗效比较差异均无统计学意义(P0.05);治疗后,2组总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)均较治疗前升高(P0.05),高密度脂蛋白胆固醇(HDL-C)较治疗前无明显变化(P0.05),2组之间TC、TG、LDL-C、HDL-C水平比较差异无统计学意义(P0.05);治疗后,2组碱性磷酸酶(ALP)、骨特异性碱性磷酸酶(BAP)、磷(P)、钙(Ca)、甲状旁腺素(PTH)水平与治疗前比较差异无统计学意义(P0.05),2组之间比较差异无统计学意义(P0.05)。结论:奥卡西平与左乙拉西坦治疗癫痫疗效相当,应用半年即有导致血脂升高,但短期应用对骨代谢影响不明显。     

地西泮联合苯巴比妥钠治疗癫痫临床效果分析

目的:探讨地西泮联合苯巴比妥钠治疗癫痫的临床治疗效果。方法:选取本院2018年1月至2021年3月收治的135例癫痫患者作为研究对象,进行回顾性分析,根据用药方案的不同分为研究组70例与对照组65例。对照组采取地西泮治疗,研究组在此基础上联合苯巴比妥钠治疗,对比两组患者临床疗效。结果:治疗前,两组患者癫痫发作频率与持续时间比较差异无统计学意义(P>0.05);经过治疗后,两组患者癫痫发作频率与持续时间均有所下降,但研究组水平相对于对照组更低(P<0.05)。研究组总有效率(95.71%)较对照组(84.62%)更高(P<0.05)。两组患者用药后均未出现明显不良反应。结论:地西泮联合苯巴比妥钠治疗癫痫可获得较好的治疗效果,不良反应较少,能够进一步控制患者病情。     

小剂量丙戊酸联合奥卡西平治疗老年癫痫46例疗效分析

目的分析小剂量丙戊酸联合奥卡西平对老年癫痫患者的疗效。方法选取92例老年癫痫患者,根据不同治疗方案将其纳入奥卡西平组(46例)与丙戊酸+奥卡西平组(46例)。奥卡西平组予以奥卡西平治疗,丙戊酸+奥卡西平组予以小剂量丙戊酸联合奥卡西平治疗。对比两组患者的癫痫发作情况(发作次数、发作持续时间)、临床疗效、脑电图变化(痫样放电、累及导联数)、脑电图改善效果。结果丙戊酸+奥卡西平组的癫痫发作次数与发作持续时间[(0.45±0.17)次/月、(1.21±0.56)分钟/次]均少于奥卡西平组[(0.86±0.33)次/月,(2.25±0.84)分钟/次)],P<0.05;丙戊酸+奥卡西平组的总有效率(93.48%)高于奥卡西平组(78.26%),P<0.05;丙戊酸+奥卡西平组治疗后脑电图的痫样放电与累及导联数[(7.38±1.43) t/180 s、(3.45±1.29)/180s]均优于奥卡西平组[(10.20±2.16) t/180s、(5.50±1.52)/180s,P<0.05];丙戊酸+奥卡西平组的脑电图总改善率(91.30%)高于奥卡西平组(73.91%),P<0.05。结论小剂量丙戊酸联合奥卡西平对老年癫痫患者的疗效显著,可明显减少癫痫发作次数与发作持续时间。     

Association of autonomic function and brain activity with personality traits by paced breathing and su-soku practice: A three-way crossover study

ObjectivesThis study aimed to compare the effectiveness of paced breathing (PB) versus su-soku practice (spontaneous breathing with counting numbers) on autonomic function and brain activity and examine the associations between personality traits, brain activity, and autonomic function.DesignA three-way crossover study design.SettingThirty healthy Korean participants (15 men: 28.5 ± 4.7 years; 15 women: 27.7 ± 4.8 years) were asked to answer the Korean version of the 125-Temperament and Character Inventory (TCI). Three-way crossover design included normal PB (0.25 Hz), slow PB (0.1 Hz), and su-soku practice. Participants were randomly assigned to one of three groups (group A: su-soku/normal PB/slow PB; group B: normal PB/slow PB/su-soku; group C: slow PB/su-soku/normal PB).Main outcome measuresThe Korean version of the 125-TCI scores, electroencephalography (EEG), heart rate variability (HRV), and respiratory curve data.ResultsEEG parameters between normal PB, slow PB, and su-soku showed no significant differences. High frequency and approximate entropy during normal PB and su-soku were higher than those during slow PB. Alpha band power related to well-focused alertness had strong negative correlations with the standard deviation of R-R intervals and square root of the mean of the sum of the squares of differences between adjacent R-R intervals during su-soku practice, while theta band power related to drowsiness had strong positive correlations with very low-frequency power during normal PB. Reflective and analytical individuals tended to be highly focused and alert during su-soku and normal PB, while anxious and unwilling individuals tended to focus on counting in and be drowsier during normal PB.ConclusionsThis study’s findings suggest that the association between brain activity and autonomic function is affected by meditation type and personality traits.     

Evaluation of an algorithm based on peripheral blood hematopoietic progenitor cell and CD34+ cell concentrations to optimize peripheral blood progenitor cell collection by apheresis

BACKGROUND: Quantification of peripheral blood (PB) CD34+ cells is commonly used to plan peripheral blood progenitor cell (PBPC) collection but is time-consuming. Sysmex has developed a hematology analyzer that can quickly identify a population of immature hematopoietic cells (HPCs) according to cell size, cell density, and differential lysis resistance, which may indicate the presence of PBPCs in PB. This prospective study has evaluated the potential of such method to predict the PBPC mobilization. STUDY DESIGN AND METHODS: A total of 141 patients underwent PBPC mobilization. PB HPCs and PB CD34+ cells were simultaneously quantified with a hematology analyzer (SE2100, Sysmex) and flow cytometry, respectively. The number of blood volumes processed was then based on PB CD34+ cell concentration. RESULTS: The optimal PB HPC level able to predict a minimal level of 10 x 10(6) PB CD34+ cells per L was 5 x 10(6) per L with positive and negative predictive values of 0.93 and 0.36 percent, respectively. For this cutoff point, sensitivity and specificity were 0.81 and 0.65, respectively. The median number of blood volumes processed according to the PB CD34+ cell count allowed us to perform only one apheresis procedure for a majority of patients. CONCLUSION: PB HPC quantification is very useful to quickly determine the initiation of PBPC apheresis especially for patients with higher concentrations. For patients exhibiting a lower HPC count (<5 x 10(6)/L), other parameters such as a CD34 test may be needed. Such a policy associated with a length of apheresis adapted to the richness in the PB CD34+ cells allows for optimizing the organization of centers with an improvement in patient comfort and economical savings.     

Continuous pentobarbital infusion in children is associated with high rates of complications

PURPOSE: To evaluate the incidence and severity of complications related to continuous pentobarbital (PB) infusion for sedation in the Pediatric Intensive Care Unit (PICU). MATERIALS AND METHODS: We conducted a retrospective, chart review study. All patients admitted to the PICU from January 1997 through June 1998 who received continuous IV PB infusion for sedation (n = 8) were included. RESULTS: All patients were intubated and mechanically ventilated prior to PB infusion. PB was used only as a second line sedative after a combination of an opioid and benzodiazepine failed to achieve adequate sedation. After initiation of PB, we were able to decrease or discontinue benzodiazepines and/or opioid doses and discontinue neuromuscular blocking drugs in all patients. We observed a high incidence of complications (62.5%) related to PB or the phenobarbital treatment used for barbiturate weaning, including blood pressure instability (25%), oversedation (12.5%), drug reaction (12.5%) and neurologic sequelae (12.5%). Discontinuation of the drug was required in 25% of the cases. CONCLUSIONS: We found continuous PB infusion to be an effective sedative for children when other drugs fail. However, we observed a high rate of clinically significant complications requiring discontinuation of the drug.     

Failure of polymyxin B nonapeptide to augment bactericidal activities of novobiocin, rifampin, and of defibrinated human blood against Serratia marcescens

Polymyxin B (PB) and polymyxin B nonapeptide (PBNP), when combined with rifampin or novobiocin, but not vancomycin, yielded additive inhibitory effects against test strains of Serratia marcescens of three varieties: those that produced cocarde growths around PB disks (coc+); those that grew adjacent to PB disks (coc-, 6); and those that yielded clear inhibition zones around PB disks (coc-, clear). However, time kill curve experiments disclosed that only the combination of rifampin + PB exerted a potent bactericidal effect against coc+ strains of S. marcescens; rifampin + PBNP and novobiocin + PB or PBNP merely effected transient decreases of colony counts. Assays involving 50% (v/v) of fresh defibrinated human blood + PB or PBNP revealed that only PB clearly augmented the antibacterial activity of blood against coc+, and less so against coc- test strains of S. marcescens.     

Detection of synergy using the combination of polymyxin B with either meropenem or rifampin against carbapenemase-producing Klebsiella pneumoniae

Polymyxin B (PB) plus meropenem (MER) or rifampin (RIF) was tested by Etest® method and time-kill assay (TKA) against 14 genetically unique clinical Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. PB + MER: Etest, 43% synergy; TKA, 64% synergy. Concordance between methods was 79%. For PB + RIF: Etest, 21% synergy; TKA, 100% synergy. Concordance between methods was 21%.     

Peripheral blood MDS score: a new flow cytometric tool for the diagnosis of myelodysplastic syndromes

BACKGROUND: Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders diagnosed using morphologic and clinical findings supported by cytogenetics. Because abnormalities may be subtle, diagnosis using these approaches can be challenging. Flow cytometric (FCM) approaches have been described; however the value of bone marrow immunophenotyping in MDS remains unclear due to the variability in detected abnormalities. We sought to refine the FCM approach by using peripheral blood (PB) to create a clinically useful tool for the diagnosis of MDS. METHODS: PB from 15 patients with MDS was analyzed by multiparametric flow cytometry using an extensive panel of monoclonal antibodies. Patterns of neutrophil antigen expression were compared with those of normal controls (n = 16) to establish light scatter and/or immunophenotypic abnormalities that correlated with MDS. A scoring algorithm was developed and validated prospectively on a blinded patient set. RESULTS: PB neutrophils from patients with MDS had lower side scatter and higher expression of CD66 and CD11a than did controls. Some MDS PB neutrophils demonstrated abnormal CD116 and CD10 expression. Because none of these abnormalities proved consistently diagnostic, we sought to increase the power of the assay by devising a scoring system to allow the association of multiple abnormalities and account for phenotypic variations. The PB MDS score differentiated patients with MDS from controls (P < 0.0001) in the test set. In a prospective validation, the PB MDS score successfully identified patients with MDS (sensitivity 73%, specificity 90%). CONCLUSIONS: FCM analysis of side scatter and only four additional immunophenotypic parameters of PB neutrophils using the PB MDS score proved more sensitive than standard laboratory approaches and may provide an additional, more reliable diagnostic tool in the identification of MDS.     

Ultrasound-enhanced thrombolysis at 20 kHz with air-filled and perfluorocarbon-filled contrast bispheres.

BACKGROUND: Ultrasound (US) at low frequencies has been shown to enhance clot lysis by itself and in the presence of urokinase (UK). The comparative effects of air-filled versus perfluorocarbon-filled polymer bispheres in enhancing this effect have not been previously demonstrated. METHODS: Freshly drawn human blood was incubated at 37 degrees C for 2 hours, and the subsequent formed clot was dried and weighed. It was then exposed to saline control, saline + UK (10,000 IU), saline + UK + US, saline + UK + US + low shell-strength polymer bispheres (PB1), saline + UK + US + high shell-strength polymer bispheres (PB2), and perfluorocarbon-filled high shell-strength polymer bipsheres (PB3) for a total of 6 minutes. Clots were removed and weighed to determine the percentage of thrombolysis. RESULTS: The percentage of clot lysis for each study group was as follows: saline 18.5% +/- 4%, US alone 22.2% +/- 5%, UK alone 21.9% +/- 4%, US+UK 32.2% +/- 8% (P <.05 compared with UK alone), US+UK+PB1 36.9% +/- 8%, US+UK+PB2 34.3% +/- 8%, and US+UK+PB3 45.0% +/- 11% (P <.05 compared with US+UK, P <.05 compared with US+UK+PB2). CONCLUSION: Ultrasound at 20 kHz significantly enhances clot lysis. The addition of perfluorocarbon-filled bispheres increased this effect more significantly than did the addition of air-filled polymer bispheres.     

苯丁酸钠通过上调p21 WAF1/CIP1基因抑制白血病细胞系的细胞周期

目的研究组蛋白脱乙酰化酶(HDAC)抑制剂苯丁酸钠(PB)对白血病细胞系细胞周期的影响,探讨其分子机制.方法PB处理白血病细胞系Kasumi-1、U937和NB4细胞,分别于处理后24,48和72 h收集细胞.碘化丙锭DNA染色,流式细胞术分析细胞周期的变化.半定量逆转录-聚合酶链反应(RT-PCR)分析细胞周期相关基因p21WAF1/CIP1表达的变化.在人肾上皮细胞系293T细胞用荧光素酶报告基因分析PB对p21WAF1/CIP1基因启动子活性的影响.结果PB可以抑制Kasumi-1、U937和NB4细胞的细胞周期,作用呈时间和剂量依赖关系.3 mmol/L PB作用72 h,分别使Kasumi-1、U937和NB4细胞的G0/G1期细胞比例增加42.03%、44.36%和26.82%,S期细胞比例减少31.86%、38.91%和26.77%.PB使Kasumi-1、U937和NB4细胞p21WAF1/CIP1表达增高.PB处理后,p21WAF1/CIP1的表达水平较处理前增高(2.06±0.27),(2.78±0.40)和(1.78±0.20)倍.PB可以上调p21WAF1/CIP1启动子的转录活性,且呈剂量依赖关系.3 mmol/L PB处理48 h使转录活性增高(5.74±0.93)倍.PB上调p21WAF1/CIP1启动子转录活性主要是依赖于转录起始位点上游101 bp的序列.结论PB可以抑制白血病细胞系的细胞周期,这种作用可能是通过上调细胞周期相关基因p21WAF1/CIP1的表达实现的.     

Antiepileptic drugs reduce the efficacy of methotrexate chemotherapy through accelerated degradation of the reduced folate carrier by the ubiquitin-proteasome pathway

Background/Aims: Concurrent treatment with methotrexate (MTX) and enzyme-inducing antiepileptic drugs including phenobarbital (PB) reduces the efficacy of MTX chemotherapy in cancer patients. We have shown that Reduced folate carrier (Rfc1)-mediated uptake of MTX, an essential determinant of MTX chemotherapy, is significantly reduced by PB via protein kinase C (PKC). However, whether PB treatment affects Rfc1 activity through regulation of carrier protein stability and the mechanisms involved remain unclear. Methods/Results: Protein turnover assays using hepatocytoma cells demonstrated that Rfc1 is a long-lived protein that is mainly degraded by the ubiquitin-proteasome proteolytic pathway under basal conditions. Pretreatment with PB significantly reduced Rfc1-mediated MTX uptake and shortened the carrier protein half-life. This effect was abolished by the specific PKC inhibitor G?6976. Inhibition of proteasomes with MG-132 significantly elevated Rfc1 protein levels and induced colocalization of Rfc1 and ubiquitin particularly in submembranous cellular compartments. Finally, we demonstrated that PB treatment resulted in enhanced levels of Rfc1 polyubiquitin conjugates. Conclusions: Our results demonstrate that PB treatment causes downregulation of Rfc1 activity through PKC-dependent accelerated degradation of the Rfc1 protein by the ubiqutin-proteasome pathway. This regulatory mechanism may therefore involve clinically relevant drug resistance in patients concurrently receiving MTX and enzyme-inducing antiepileptic drugs.     

Kinetics of drug action in disease states. I. Effect of infusion rate on phenobarbital concentrations in serum, brain and cerebrospinal fluid of normal rats at onset of loss of righting reflex

The purpose of this investigation was to develop a method to determine the effect of various diseases on the concentration-pharmacologic activity relationship of phenobarbital (PB) in a manner that excludes or accounts for pharmacokinetic variables affecting drug disposition. Adult female rats (congruent to 180 g) received an i.v. infusion of PB at one of five different rates (0.412-4.12 mg/min) until the animals lost their righting reflex (after 8.0 +/- 0.4 to 62 +/- 10 min of infusion). The total dose, the serum concentration (both total and unbound drug) and the brain concentration of PB at onset of loss of righting reflex (LRR) increased with increasing infusion rate. The PB concentration in cerebrospinal fluid at onset of LRR (mean +/- S.D.: 108 +/- 19 micrograms/ml, n = 29) was not affected by the infusion rate. Concomitant infusion of PB and its p-hydroxy metabolite had no apparent effect on the concentrations of PB at onset of LRR even though the serum concentration of p-hydroxy PB was higher than upon infusion of PB only. The results of this investigation indicate that cerebrospinal fluid, unlike some regions of the brain, equilibrates very rapidly with the biophase of the receptors for PB-induced LRR. Determination of PB concentrations in the cerebrospinal fluid at the onset (rather than offset) of action facilitates assessment of the effect of diseases on the PB concentration-pharmacologic activity relationship by avoiding development of acute tolerance and excluding or minimizing effects due to disease-associated pharmacokinetic variables such as altered plasma protein binding and body distribution of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)