ライフサイエンスコーパス: peripherally

1 ol of the animal body by this microbe occurs peripherally.

2 n though the stimulus was unseen and located peripherally.

3 mediated via the TRIF pathway when delivered peripherally.

4 d improved leptin action, both centrally and peripherally.

5 uodenal cellular responses was not reflected peripherally.

6 patic or perihilar, and a mixed form located peripherally.

7 elay significantly shorter than when applied peripherally.

8 educed transcription from alleles positioned peripherally.

9 redominates centrally and rod loss increases peripherally.

10 sthetic duration when delivered centrally or peripherally.

11 tional TLR4 when administrated centrally and peripherally.

12 (Pe327; 7.2 pmol/kg/min; n = 5) was infused peripherally.

13 the insulin-induced mechanical sensitization peripherally.

14 be membrane-associated either integrally or peripherally.

15 that regulation of humoral responses occurs peripherally.

16 nt of the image; this difference was greater peripherally (6.02 mum) than centrally (2.54 mum).

17 There were 48 nodules located peripherally (85.71%).

18 In contrast, repeated injections of the peripherally acting analog of nicotine, nicotine pyrroli

19 cerns that underscore the need for effective peripherally acting drugs.

20 Peripherally acting mu-opiate antagonists are another op

21 ed the efficacy and safety of naldemedine, a peripherally acting mu-opioid receptor antagonist, for t

22 e efficacy and safety of naloxegol, an oral, peripherally acting, mu-opioid receptor antagonist, for

23 eptor blockade in the brain, suggesting that peripherally-acting only CB1 receptor blockers may be us

24 that disease is mediated by antigen-specific peripherally activated CD4(+) T cells that infiltrate th

25 everal advantages over previously identified peripherally active cannabinoid compounds, and could hav

26 inct from these holds promise for developing peripherally active CB1 inverse agonists with fewer side

27 ophilicity compared to rimonabant to achieve peripherally active molecules with minimal central effec

28 ed as "active" (DVR highest in the lesion), "peripherally active" (perilesional DVR highest), "inacti

29 Here, we show that newly designed peripherally active, potent, and selective kappa-opioid

30 r enhancing clearance of plasma Abeta with a peripherally administered Abeta-degrading protease would

31 tenuates the intake-suppressive effects of a peripherally administered amylin analog, suggesting that

32 Peripherally administered antibodies against NPCT decrea

33 Peripherally administered ghrelin in liver, heart, and a

34 e, but found that they responded normally to peripherally administered GLP-1 and exendin-4.

35 systemically in humans, we evaluated whether peripherally administered GLP-1R agonists access the LDT

36 linical trials by others show that repeated, peripherally administered high doses of recombinant NT3

37 Here we report that peripherally administered leptin-P85 conjugates exhibit

38 M) activates FGF receptors, we asked whether peripherally administered NCAM peptide mimetics penetrat

39 does not unequivocably demonstrate that the peripherally administered OT is entering the CSF.

40 Peripherally administered prolactin rapidly activates br

41 Rather, peripherally administered TAM-163 localized to areas in

42 These data suggest a clear effect of a peripherally administered, Food and Drug Administration-

43 interleukin-27 is upregulated centrally and peripherally after intracerebral hemorrhage.

44 alizing mRNA until its release from the mRNA peripherally, allowing ribosome binding.

45 is predominantly localized to the cell body peripherally along the Golgi zone.

46 Finally, it is shown that such peripherally and binding pocket-modified vancomycin anal

47 eripheral effects, by administering oxytocin peripherally and by blocking peripheral actions with ant

48 inflammatory and nociceptive mediators both peripherally and centrally in sickle mice correlative to

49 olyclonal antibodies, act as immunomodulator peripherally and centrally, and it can reduce amyloid pa

50 mu-Opioid receptors (MORs) are expressed peripherally and centrally, but the loci of MORs respons

51 ansmitter system that controls gut functions peripherally and centrally.

52 enon did not differ between attacks starting peripherally and centrally.

53 liver and high free exposures of drug, both peripherally and in the CNS.

54 s and contribute to motivated behavior, both peripherally and within the central nervous system (CNS)

55 es to polyclonal TCR stimulation are present peripherally and within the lungs of sarcoid patients.

56 t appears to be selective for Adelta-fibers (peripherally) and HT neurons (centrally).

57 to be even more drastic in the case of their peripherally annulated counterparts.

58 associated with an increasing proportion of peripherally, as opposed to perinatally derived AMs.

59 CD8alphaalpha T cells are found to circulate peripherally, as well as reside within the lymphoid tiss

60 and ClpP3/ClpP4/ClpP5/ClpP6 (the P-ring) and peripherally associated ClpT1/ClpT2 subunits.

61 Annexin A2 (AnxA2) is a peripherally associated membrane protein that can suppor

62 Here we analyzed the ability of one peripherally associated membrane protein, annexin A2 (An

63 ns; thus, its shape and size are governed by peripherally associated membrane proteins and possibly b

64 ne association is readily apparent, but many peripherally associated membrane proteins are outwardly

65 ntirely by phylum-specific components, and a peripherally associated subcomplex contributes to the me

66 ses revealed that SYNV sc4 and TYMaV P3 were peripherally associated with cell membranes.

67 dynamic equilibrium: one in which zetacyt is peripherally associated with lipid headgroups and one in

68 The eisosome portion includes proteins peripherally associated with the cytoplasmic side of the

69 ary protein components such as M1 and NP are peripherally associated with the membrane.

70 somehow be presented to a series of enzymes peripherally associated with the mitochondrial inner mem

71 s simplex virus (HSV-1) infects when applied peripherally at an epithelial surface that had been trea

72 er cells as a remnant that initially locates peripherally at the apical surface of one of the daughte

73 Oligomers of membrane-embedded caveolins and peripherally attached cavins form the caveolar coat whos

74 be used to modulate touch and may represent peripherally available drugs to treat tactile-driven pai

75 Such an equilibrium between the peripherally bound and embedded forms of zetacyt apparen

76 The peripherally bound, rapidly exchanging tetraphenylborate

77 measurements, have been used to estimate HRV peripherally but decline in accuracy during increased ph

78 Other large cells arise more peripherally by initiating endocycles and becoming polyp

79 lucose metabolism, whereas insulin delivered peripherally cannot act on the liver without also affect

80 e that a TrkB agonist antibody, administered peripherally, causes species-dependent effects on body w

81 ease), indication for insertion (infusion of peripherally compatible infusates vs. vesicants), and du

82 For peripherally compatible infusions, PICC use was rated as

83 iol-ending-polyamido-based dendron (d-BAPAD) peripherally decorated with amoxicilloyl (AXO) groups (d

84 e haloperidol's activity either centrally or peripherally, dependent on the location of administratio

85 ated a temporally restricted accumulation of peripherally derived CCR2(+) macrophages, which were con

86 VA-Sp administration increased MPO-specific, peripherally derived CD4(+)Foxp3(-) type 1 regulatory T

87 ussed are recent findings demonstrating that peripherally derived endocrine signals act on receptors

88 s substantial reductions in gut-resident and peripherally derived Foxp3(+) Treg cells.

89 motif) ligand 2 (CCL2), a greater number of peripherally derived immune cells accumulating in the ol

90 interfaces elicit stromal cell infiltration, peripherally derived inflammation, neural damage and amy

91 Central nervous system resident and peripherally derived inflammatory cells respond to TBI a

92 mpaired the development and function of both peripherally derived iTregs and in vitro-induced Tregs.

93 -dominant response occurred in microglia and peripherally derived macrophages as remyelination starte

94 se from resident microglia and infiltrating, peripherally derived monocytes.

95 replaced the pool of resident microglia with peripherally derived myeloid cells in Abeta-carrying APP

96 cells with amyloid plaques neither directed peripherally derived myeloid cells to amyloid plaques no

97 owed by a rapid repopulation of the brain by peripherally derived myeloid cells.

98 Peripherally derived regulatory T (pT(reg)) cell generat

99 ed in a marked reduction in both thymus- and peripherally derived Tregs, accompanied by the developme

100 specific demethylation and also induction of peripherally derived Tregs.

101 action, and, ultimately, regulates local and peripherally-derived immune cells to provide a supportiv

102 to thymus-derived natural Tregs (tTregs) and peripherally-derived induced Tregs (pTregs).

103 TBI-induced activation of microglia and peripherally-derived inflammatory macrophages may lead t

104 as been no demonstration of proliferation of peripherally-derived inflammatory macrophages under phys

105 ic functional parameters of brain populating peripherally-derived myeloid cells and endogenous microg

106 While peripherally-derived myeloid cells exhibited increased p

107 nd response to CNS injury of newly recruited peripherally-derived myeloid cells.

108 incidence of pulmonary embolisms, generally peripherally distributed and associated with endothelial

109 ch less, the actin is centrally, rather than peripherally distributed and the edge dynamics is largel

110 These findings demonstrate that the peripherally distributed octopus nervous system is a key

111 How the peripherally distributed octopus nervous system mediates

112 Peripherally disulfonated BODIPY photocages are cell imp

113 e anorectic and glucose tolerance effects of peripherally dosed GLP-1RA exendin-4 and liraglutide wer

114 closely associated with neurites projecting peripherally during formation of the vestibular and coch

115 their olfactory organs with the potential to peripherally encode temporal information about odor enco

116 t that histamine itch and capsaicin pain are peripherally encoded in C-MIAs, and that primate polymod

117 nity but also for inducing tolerance against peripherally encountered antigens such as tissue-specifi

118 ion and identify GINIP as a key modulator of peripherally evoked GABAB-receptors signaling.

119 em of rodents is an excellent model to study peripherally evoked neural activity in the brain.

120 em of rodents is an excellent model to study peripherally evoked neural activity in the central nervo

121 EAAT4 reporter transgenic mice, we show that peripherally evoked patch-like responses in Crus II are

122 Infiltration of the lamina propria by peripherally expanded CD8(+) T cells was observed after

123 ular pathway that restricts proliferation of peripherally expanded naive T-cell clones that accumulat

124 ith CD31 expression and thus is decreased in peripherally expanded naive T-cell clones.

125 but maintain efficacy through antagonism of peripherally expressed CB1 receptors.

126 Glucagon-like peptide-1 (GLP-1) is both a peripherally expressed incretin and a centrally active n

127 loiting the crystallization conditions for a peripherally extended triptycene H(6) PET, we can modula

128 Peripherally, Flx has anti-resorptive properties, direct

129 verlaps significantly with many conventional peripherally-focused neuromodulatory therapies.

130 ivery are those capable of inducing benefits peripherally following intravenous injection and in the

131 In summary, the study of peripherally functionalised multiple bonds with heavier

132 ers are replaced by metal-organic polyhedra, peripherally functionalized so as to have the same conne

133 sed chromophore, composed of a borazine core peripherally functionalized with azobenzene moieties.

134 sease onset and perpetuation are mediated by peripherally generated autoreactive T cells infiltrating

135 sions demonstrate that PFs contribute to the peripherally generated responses in Crus I.

136 The peripherally grafted, green fluorescent protein-labelled

137 iation (0.13 mum/yr centrally vs 0.06 mum/yr peripherally); however, average, normalized GCL loss per

138 TREM1 was induced within hours after stroke peripherally in CD11b(+)CD45(+) cells trafficking to isc

139 pattern that was sparse centrally and peaked peripherally in healthy human eyes.

140 ological alterations occurring centrally and peripherally in PD.

141 after the administration of different doses peripherally in rats.

142 itochondria that are motile are located more peripherally in the cell than non-motile mitochondria.

143 Together with the peripherally induced Ag-specific Foxp3(+) Treg cells, th

144 and dependent on IL-10 and thymic as well as peripherally induced Ag-specific Treg cells.

145 nted central nervous system infiltrating and peripherally induced antigen-specific TH17 cells.

146 Notably, peripherally induced brain T(RM) cells showed evidence o

147 Thymus-derived Tregs (tTregs) and their peripherally induced counterparts (pTregs) are imprinted

148 ved IL-10, and Ag-specific thymic as well as peripherally induced Foxp3(+) regulatory T (Treg) cells.

149 blation of NMBR neurons partially attenuated peripherally induced itch without compromising nocicepti

150 o sensory ganglia dramatically reduced acute peripherally induced nociception and alleviated neuropat

151 on neurons in vivo reduced acute and chronic peripherally induced nociception.

152 to sensory ganglia triggered or exacerbated peripherally induced nociception.

153 Both spinally and peripherally induced priming is prevented by intrathecal

154 a privileged site for the generation of both peripherally induced regulatory CD4(+) T cells (Tregs) a

155 nd a significant increase in the quantity of peripherally induced regulatory donor T (pTreg) cells in

156 Foxp3 and limit the inopportune induction of peripherally induced regulatory T cells during immune re

157 regulatory T cells, which have a natural and peripherally induced subset, IL-17 production by iNKT ce

158 luding butyrate facilitate the generation of peripherally induced T(reg) (pT(reg)) cells(5-7), indica

159 dependent differentiation of T(EFF) cells to peripherally induced T(REG) and T(H)17 cells.

160 iated with CD103(+) dendritic cells, such as peripherally induced Treg development or imprinting CCR9

161 ammation in extraintestinal tissues, whereas peripherally induced Tregs retained in the absence of B7

162 addition to Th17 cells, is also expressed in peripherally induced, colonic regulatory CD4(+) T cells.

163 also be imprinted in natural iNKT17 cells or peripherally induced.

164 nction and stability of both thymically- and peripherally-induced Treg cells.

165 main TLR9-responsive cell and accumulated in peripherally inflamed tissues during TLR9-driven inflamm

166 , these findings support our hypothesis that peripherally injected alphaviruses enter the CNS by hema

167 xamined its role for the febrile response to peripherally injected lipopolysaccharide.

168 ntral 5-HT2A receptors are also required for peripherally injected liraglutide to reduce feeding and

169 s of studies was completed in mice that were peripherally injected with lipopolysaccharide and later

170 microglia around the central projections of peripherally injured Ia afferents, suggesting a possible

171 post-CPG group were less likely to receive a peripherally inserted central catheter (2.5%, n = 3 vs 3

172 differences were found using single-lumen 4F peripherally inserted central catheter (mean cardiac ind

173 r-immobilized, liquid perfluorocarbon-coated peripherally inserted central catheter (PICC) line and i

174 e administered orally or intravenously via a peripherally inserted central catheter (PICC).

175 ements obtained with bolus injection through peripherally inserted central catheter and centrally ins

176 Bolus injection through peripherally inserted central catheter for transpulmonar

177 The rate of peripherally inserted central catheter line complication

178 ly higher when measured with double-lumen 5F peripherally inserted central catheter than with central

179 ither a single-lumen 4F or a double-lumen 5F peripherally inserted central catheter using were compar

180 olume index, especially when double-lumen 5F peripherally inserted central catheter was used (Clinica

181 No overdoses, deaths, or peripherally inserted central catheter-line complication

182 ntral-line associated bloodstream infection (peripherally inserted central catheter: 0.73%, central v

183 An increased rate of venous thromboembolism (peripherally inserted central catheter: 0.93%, central v

184 central venous catheter: 0.24%; p = 0.001) (peripherally inserted central catheter: 10.82/1,000 line

185 central venous catheter: 0.52%; p = 0.001) (peripherally inserted central catheter: 8.65/1,000 line

186 common catheters inserted were single-lumen peripherally inserted central catheters (n = 1,653; 36.3

187 laboratory tests, parenteral nutrition (PN), peripherally inserted central catheters (PICC), and hosp

188 d whether red blood cell transfusion through peripherally inserted central catheters (PICCs) affects

189 Peripherally inserted central catheters (PICCs) are a co

190 Peripherally inserted central catheters (PICCs) are asso

191 Is parenteral nutrition via peripherally inserted central catheters (PICCs) associat

192 Use of peripherally inserted central catheters (PICCs) has grow

193 commendations, endorse avoiding placement of peripherally inserted central catheters (PICCs) in patie

194 Among CVCs, the number of peripherally inserted central catheters (PICCs) placed h

195 to growing demand, and possible overuse, of peripherally inserted central catheters (PICCs).

196 ity within Australia, most other centres use peripherally inserted central catheters (PICCs).

197 included 74,196 first lines including 4,493 peripherally inserted central catheters and 66,194 centr

198 Central venous access devices, including peripherally inserted central catheters and central veno

199 Peripherally inserted central catheters are associated w

200 Peripherally inserted central catheters are increasingly

201 catheter: 4.97/1,000 line days) occurred in peripherally inserted central catheters.

202 5% CI, 0.330-0.982; p = 0.043) compared with peripherally inserted central catheters.

203 Peripherally inserted central venous catheters (PICCs) a

204 Newborn babies who needed a peripherally inserted CVC (PICC) were allocated randomly

205 selective TLR4 antagonist, was administered peripherally (intravenous) and centrally (intracerebrove

206 Whereas NAP acted mainly peripherally, its derivatives NFP and NYP actually can a

207 hypothesis here that overexpression of BDNF peripherally leads to a disrupted terminal field organiz

208 A third subpopulation, constituting the most peripherally localized bacteria, directly contacted neut

209 We developed new tools to quantify peripherally localized early endosomes and measure the r

210 ls generate stronger, less dynamic, and more peripherally localized traction forces.

211 in case of impaired hypoglycemia sensing by peripherally located glucose detection systems that are

212 ulmonary lesions) had pleural origin or were peripherally located in the lung with a small amount of

213 lgesic effect is attributed to activation of peripherally located kappa receptors, since 14b did not

214 ns that are innervated by efferents in their peripherally located parts, and efferents also innervate

215 kinesin-1 motors, which transport LDs to the peripherally located smooth ER inside hepatocytes, where

216 As development progresses, most oriCs become peripherally located.

217 displayed a lower inflammatory status, both peripherally (lower levels of circulating cytokines) and

218 Limited bedding impaired peripherally-measured basal corticosterone in adult male

219 M1 is peripherally membrane associated, whereas NP associates

220 f SpoIVFB, a portion of the Pro-sigma(K) was peripherally membrane associated.

221 These peripherally membrane-anchored virulence factors mediate

222 ransform infrared measurements show that the peripherally membrane-bound cyt-c experiences significan

223 nd thioamide) are disclosed as well as their peripherally modified (4-chlorobiphenyl)methyl (CBP) der

224 t combined binding pocket and chlorobiphenyl peripherally modified analogues exhibit a remarkable spe

225 dicates that combined pocket amidine and CBP peripherally modified analogues exhibit a remarkable spe

226 rt the first solution recognition studies of peripherally NBN-doped PAHs to form H-bonded DD.AA- and

227 out (KO) and/or wild-type mice were injected peripherally or intracerebroventricularly with ghrelin a

228 d portally (PoHI; 1.8 pmol/kg/min; n = 7) or peripherally (PeHI; 1.8 pmol/kg/min; n = 8) and insulin-

229 demonstrate the ability of a small number of peripherally placed sources to generate acoustic vortex

230 that the MEK inhibitor PD325901 administered peripherally prior to cocaine SA increased cocaine intak

231 study, we analyzed whether CT-1 also acts to peripherally regulate metabolic rhythms and adipose tiss

232 lls, probably in concerted action with other peripherally released cytokines.

233 The rich repertoire of peripherally released peptides and hormones provides fee

234 rchestrate metaflammation both centrally and peripherally remains incompletely understood.

235 Conversely, peripherally-responsive primary visual cortex demonstrat

236 Linaclotide, a peripherally restricted 14 aa peptide approved for the t

237 suggesting poor BBB penetration and possible peripherally restricted activity.

238 n of fibers may allow for the development of peripherally restricted analgesics that control BTP and

239 -cyclohexyl]-3-pyr idinecarboxamide] and its peripherally restricted analog 14H: [5-(4-chlorophenyl)-

240 orted herein with the objective of producing peripherally restricted analogues.

241 Difelikefalin is a peripherally restricted and selective agonist of kappa o

242 In preclinical models, peripherally restricted cannabinoid receptor type 1 (CB1

243 diet-induced obesity (DIO), using JD5037, a peripherally restricted CB1 R inverse agonist.

244 Similarly, a neutral, peripherally restricted CB1 receptor antagonist (AM6545)

245 Peripherally restricted CB1 receptor antagonists may be

246 ins iNOS inhibitory activity, and JD-5037, a peripherally restricted CB1R antagonist, were used to as

247 entification of compound 4 (B/P = 1/64) as a peripherally restricted CB1R antagonist.

248 rt the rationale for the clinical testing of peripherally restricted CB1R antagonists or the developm

249 of the highly potent, kinase-selective, and peripherally restricted clinical candidate PF-06273340.

250 Our SAR studies generated a new series of peripherally restricted FAAH inhibitors and identified c

251 Moreover, acute treatment with a peripherally restricted GABA(A) receptor agonist that ac

252 ere treated for 14 days with (S)-MRI-1867, a peripherally restricted hybrid inhibitor of CB1R and iNO

253 dies of ABHD6, including brain-penetrant and peripherally restricted inhibitors that should prove of

254 In addition, the peripherally restricted molecule 22 also demonstrated si

255 dministration of methylnaltrexone bromide, a peripherally restricted MOR antagonist, was sufficient t

256 laxatives, new intestinal secretogogues, and peripherally restricted mu-opiate receptor antagonists,

257 pain pathways moreover the importance of non-peripherally restricted Na(V) isoforms in pain generatio

258 agonists naloxone and naloxone methiodide (a peripherally restricted naloxone analog) and by local ad

259 inflammatory models, acute administration of peripherally restricted NaV1.7 inhibitors can only produ

260 Thus, PG-M may serve as prototype of a peripherally restricted opioid formulation designed to f

261 s, our results suggest that the long-acting, peripherally restricted OTR agonist may offer potential

262 Administration of a peripherally restricted oxytocin receptor antagonist did

263 These were peripherally restricted via drug pumps that limit the CN

264 d classified as either "brain penetrant" or "peripherally restricted" on the basis of the experimenta

265 the latter which is commonly believed to be peripherally restricted, affect brain oxygen responses i

266 overy of a highly potent, subtype selective, peripherally restricted, efficacious, and well-tolerated

267 In this work, we describe the discovery of a peripherally restricted, potent, competitive NMDA recept

268 Furthermore, OT-12 is peripherally restricted, with very limited brain exposur

269 algesics with mixed-opioid agonist activity, peripherally selective activity is expected to decrease

270 r latest results toward the development of a peripherally selective analog of the diphenyl purine CB1

271 nt's withdrawal, several groups are pursuing peripherally selective CB1 antagonists.

272 Orally bioavailable and peripherally selective compounds have been produced that

273 ate planar heterojunction devices comprising peripherally substituted subphthalocyanines as acceptors

274 position of two subphthalocyanines (SubPcs) peripherally substituted with hydrogen (H12SubPc) or flu

275 oligothiophene electron donor cores that are peripherally substituted with naphthalene diimide electr

276 This was particularly the case for peripherally targeted dendritic inhibition where dynamic

277 n be treated using CGRP antagonists that act peripherally, the relevant sites of CGRP action remain u

278 arcellating the processing of semiochemicals peripherally, these odorants may be processed in a more

279 ulate systemic metabolism both centrally and peripherally through secretion of adipocyte-derived pept

280 saccharide (LPS) or vehicle was administered peripherally to adult zebra finches and sickness behavio

281 the membrane but rather attaches the protein peripherally to endoplasmic reticulum membranes.

282 derived hypothalamic islets can be implanted peripherally to enhance general health and survival toge

283 ecent results suggest that the protein binds peripherally to membranes containing negatively charged

284 ere loaded with glucocorticoids and injected peripherally to modify the infiltrated CD163 cells towar

285 We also uncovered that Unc-4 acts peripherally to promote proprioceptive sensory organ dev

286 r aorta and pulmonary artery are anastomosed peripherally to the femoral artery and vein of the recip

287 Rather, it forced blood to flow peripherally to the gel.

288 ers formed by nonideal lipid mixing, binding peripherally to the lipid headgroups with minimal pertur

289 continuum-from those whose pain is generated peripherally to those whose pain is centralized (i.e., g

290 2 leaves this signaling complex and migrates peripherally together with vinculin to the membrane lead

291 Peripherally triarylborane decorated porphyrin (2) and i

292 uman insulin (HI) delivered intraportally or peripherally were compared with an acylated insulin mode

293 ntinuously presented native Chinese speakers peripherally with Chinese homophone characters in an odd

294 or wild-type (WT) littermates were injected peripherally with lipopolysaccharide (LPS), a bacterial

295 id binding protein, interacts reversibly and peripherally with liposomal NPs without experiencing sig

296 BORC associates peripherally with the lysosomal membrane, where it funct

297 ronatin has also been shown to be translated peripherally within the dendrites of neurons, a finding

298 Thus, MDP scaffolds delivered centrally and peripherally within whole dental pulp tissue are shown t

299 lst the thick/thin filament lattice can form peripherally without a Z-disc.

300 tory neuroepithelium to the TG and reemerged peripherally without causing significant neurological di