Patients treated using the new IM sedation protocol were compared to historical

controls. The historical controls were taken from the period prior when the existing practice was to predominantly use IV sedation. The structured IM sedation protocol was introduced as part of a clinical trial comparing droperidol (10 mg), midazolam (10 mg) and a combination of droperidol (5 mg) and midazolam (5 mg). The clinical trial is described in detail elsewhere. Ethics approval was obtained for the historical control study from the Human Research Ethics Committee. The hospital where the study was undertaken has a tertiary toxicology unit, and although there are only 27,000 presentation to the ED OTX015 solubility dmso annually, there is a high proportion Inhibitors,research,lifescience,medical of patients with agitation, delirium, Inhibitors,research,lifescience,medical aggression and acute behavioural disorders because the hospital provides a regional clinical toxicology service and Drug and Alcohol Unit[2]. Selection of Participants The study compared patients treated with the new structured IM sedation protocol during an eight month period from August 2008 to March 2009 to a group of historical control patients sedated Inhibitors,research,lifescience,medical in the ED in the eight month period immediately before the protocol was introduced (November 2007

to June 2008). The structured IM sedation protocol consisted of: 1.An intramuscular injection of the clinical trial drug, which was labelled and kept in the ED. 2.A defined approach to monitoring of the patient’s vital signs over a six hour period 3.The introduction and use of a sedation score to be included as part of the standard observation of the patient 4.Recording of further Inhibitors,research,lifescience,medical sedation, adverse events, staff or patient injury for all patients. 5.Route and type of additional sedation

was dictated by the treating clinician. Inclusion criteria for both the historical controls (use Inhibitors,research,lifescience,medical of predominantly IV parenteral sedation) and the intervention group (IM sedation only) were that the patient required both physical and chemical restraint, the patient did not consent to IV or oral sedation and they required the presence of the hospital security. To identify and ensure that the historical control group was similar to patients during the new IM sedation protocol we accessed the hospital security log for both time periods. The security log documents all security responses to ABD in the ED and has previously Parvulin been shown to be the most accurate record of patients with ABD[2]. Medical records were retrieved for all patients who had required security to attend the ED and only patients meeting the inclusion criteria were included. Exclusion criteria were successful verbal de-escalation, agreement to oral or IV sedation, previous administration of other sedative medication or the patient did not remain in the ED (escorted off premises by police, absconded) (Figure ​(Figure11).

For example, Benedix et al. (18) demonstrated that right-sided tumors tended to occur in older women with more co-morbidities. These tumors tended to show a more poorly differentiated histology and there was an overall worse prognosis

in patients with RCC as compared to LCC. Mequid et al. using retrospective survival analysis of data from the Lenvatinib research buy Surveillance, Epidemiology, and End Results Program (SEER) database between 1988 and 2003, showed that RCC had a 5% increased mortality risk relative to LCC (19). The Mequid study treated many of the parameters observed by the Benedix group as confounders, and as such, Inhibitors,research,lifescience,medical more stringently controlled for age, gender, race, tumor stage, tumor size, histologic grade, number of lymph nodes examined, and year of diagnosis. From these two studies, it appears

there is a difference in behavior of RCC and LCC, but it is not precisely clear what the extent of the difference is. Other studies appear to contradict these reports, although they also Inhibitors,research,lifescience,medical have shown differences in morbidity and mortality between patients with right-sided versus left-sided cancers. Weiss et al. also used SEER data to show that there was no Inhibitors,research,lifescience,medical statistically significant difference in mortality between RCC and LCC for all stages combined and for stage I disease. However, there was a significant decrease in mortality seen with stage II RCC as Inhibitors,research,lifescience,medical compared to LCC. This is in

contrast to an increased mortality seen in stage III right-sided cancers when compared to the left colon (17). In addition, this group performed an extensive adjustment of confounding factors as well as limiting the sample to a more homogenous group of patients with a narrow age distribution (66 years and older as a result of Medicare linkage) and those considered for surgery with curative therapy (by excluding AJCC stage IV and those undergoing palliative procedures). While this body of literature implies differences Inhibitors,research,lifescience,medical in tumor biology based on anatomic location, it does not either unambiguously define those differences. More studies are necessary to fully elucidate the phenomenon in question. Molecular basis of colorectal cancer Differences between right- and left-sided colorectal cancers are observed at the molecular level as well as the gross anatomic level. The primary mechanism through which molecular alterations lead to colorectal cancer appears to be genomic instability. Genomic instability may take a number of forms which are generally classified as chromosomal instability, DNA-repair defects, and aberrant DNA methylation (20). Chromosomal instability is the most common type of genomic instability associated with the development of colorectal cancers. These somatic defects are characteristic of roughly 80-85% of sporadic colorectal cancers (20).

In the last 20 years, 256 cases of the central nervous system hydatid cyst have been published from Iran. This cyst site accounted for the third common site of the hydatid cyst after the lung and liver. The hydatid cyst of the spinal cord is less common. According to the recent literature, this cyst accounts for about 1% of all the cases of the hydatid cyst.29 In this location, the intravertebral discs are usually preserved because the disease

tends to progress beneath the periosteum and BKM120 datasheet ligaments.29 The orbital hydatid cyst accounts for about 1-2% of the cases in the previous literature and is most commonly detected in childhood.158 Our survey yielded 36 cases of the orbital hydatid Inhibitors,research,lifescience,medical cyst published from Iran.15,26,27 Musculoskeletal System Osseous hydatid disease and muscular hydatidosis are uncommon and account for 0.5-4% and 0.5-2.5% of all hydatidosis cases, respectively (in endemic areas).159 The most common locations of the osseous hydatid cyst are the vertebra, pelvis, and long bones Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical in the previous records from other parts of the world.41 However, in the published cases form Iran, there were 55 cases with variable locations such as the long bone, mandible, maxilla, and pelvis.38-54 Muscle involvement of the hydatid cyst is reported as an uncommon location, because of high lactic acid, which is not a suitable environment for the parasite.58 Cardiovascular

System The heart and large blood vessels also have been reported as the common unusual body sites of the hydatid cyst in endemic areas of the world, Inhibitors,research,lifescience,medical accounting for 0.5-2% of all the reported cases.160 The diagnostic method unique for this part of the body is echocardiography, which has been claimed as the method of choice for the diagnosis of the cardiac hydatid cyst. Nonetheless, CT scan and MRI are also helpful in other parts of the body.161 Kidney and Urinary Tract The kidney is the most common location

in the urinary tract and has been reported Inhibitors,research,lifescience,medical in about 2-3% of all cases of the hydatid cyst.83 In many of the previous reports from DNA ligase other parts of the globe, the kidney is reported as the third common site of the hydatid cyst after the liver and lung.162-164 In our survey of the published cases from Iran, however, the renal hydatid cyst was the fourth most common location of the hydatid cyst. The clinical symptoms are nonspecific, and the only interesting and diagnostic symptom reported is hydatiduria.163 The hydatid cyst of the urinary bladder is even less common, and only 2 cases were published from Iran.6,86 This cyst can also present with hydatiduria and is, otherwise, extremely difficult to diagnose before surgery.164 Spleen Less than 2-5% of the cases of the hydatid cyst have been reported from the spleen.165 There were 20 cases of the splenic hydatid cyst published from Iran.

Dai et al. combined targeted delivery with antineoplastic and antiangiogenic agent delivery in PEGylated liposomes [255]. Coloading of the antiangiogenic agent combretastin A-4 in the lipid bilayer and the anticancer drug doxorubicin in the aqueous core of PEGylated liposomes resulted in increased therapeutic activity. Hu et al. also combined liposomal Inhibitors,research,lifescience,medical delivery of the antineoplastic and antiangiogenic agent, honokiol with irradiation for maximal therapeutic efficacy [256]. They hypothesized that this protocol would combine the destruction of

tumor cells by irradiation with inhibition of irradiation-induced neoangiogenesis by honokiol [257]. The combination of PEGylated honokiol-loaded and radiotherapy showed increased survival of Lewis lung carcinoma-bearing

mice compared to radiotherapy or honokiol liposomes alone, resulting in decreased angiogenesis Inhibitors,research,lifescience,medical in vivo. Maitani et al. also combined an antineoplastic drug (irinotecan) and an antiangiogenic agent (sunitinib) [258]. The drug combination had more therapeutic efficacy against pheochromocytoma neuroendocrine tumors in vivo when they were administered as sunitinib liposomes plus irinotecan liposomes or as coloaded liposomes than the combination of the free drugs, with higher drug accumulation as liposomes Inhibitors,research,lifescience,medical than as free drug. In a similar fashion, folate-targeted doxorubicin-loaded liposomes coloaded with a bifunctional peptide capable of vascular disruption and antitumor activity were more effective against KB human nasopharyngeal carcinoma in vivo than untargeted coloaded liposomes than either monotherapy

Inhibitors,research,lifescience,medical [259]. RGD-targeted liposomes coloaded with doxorubicin and the vascular disrupting drug combrestatin A-4 increased Inhibitors,research,lifescience,medical tumor regression of B16F10 melanoma compared to untargeted coloaded liposomes or targeted liposomes with either drug [260]. Zucker and coworkers have optimized the simultaneous loading of vincristine and topotecan into PEGylated liposomes (LipoViTo liposomes) and provided the reader with the methods needed to characterize a liposomal drug combination [261]. Use of LipoViTo increased buy Talazoparib 100-fold only the drug distribution to tumors compared to free drug and led to superior therapeutic efficacy over a free drug combination or liposomes with a single drug. PEGylated liposomes containing both vincristine and quercetin allowed reduced blood clearance of both drugs in mice, increased the therapeutic activity over a combination of free drugs and decreased side-toxicity [262]. Celator Pharmaceuticals Inc. (Princeton, NJ) developed a liposomal formulation of cytarabine: daunorubicin (CPX-351, 5:1 molar ratio) [24, 263, 264].

47 Host genetic factors appear to play a key role, with a large British study reporting a significantly higher concordance rate of certain phenotypic characteristics among monozygotic compared with dizygotic twins (60% to 92% versus 0% to 10%).48 MAPK Inhibitor Library supplier Genome-wide association studies have revealed a number of loci strongly associated with ASDs, including those involved in synaptogenesis and synaptic function (eg, neurexins and the neuroligins that bind them49,50). Although heritability in the British twin study was calculated to be >90%, environmental influences may be still considerable. Inhibitors,research,lifescience,medical A “gut-brain” linkage for ASDs has been proposed, based in part on reports

that children with ASDs often experience a range of gastrointestinal disorders. 51,52 A few reports indicate that children with ASDs have a greater representation of members of the bacterial family Clostridiales51-53 in their fecal microbiota, although as noted below, comprehensive analyses of gut microbial ecology in Inhibitors,research,lifescience,medical affected and reference control populations have not yet appeared in the literature. Microbial metabolism may have an impact on disease pathogenesis in ASD. Initial evidence for Inhibitors,research,lifescience,medical this came from a small study of

autistic children treated with the minimally absorbed glycopeptide antibiotic vancomycin; short-term improvement was reported,54 leading to the suggestion that autistic symptoms may be related to the production of neurotoxic metabolites by the gut microbiota. Two subsequent studies of metabolites in urine Inhibitors,research,lifescience,medical have supported that microbial metabolism results in altered metabolite profiles in children with ASD. The application of pattern recognition analysis to compare 1H-NMR spectra from the urine of

children with ASD to their relatives and age-matched controls indicated that among the metabolites that changed in concentration with autism were mammalian-microbial cometabolites, including dimethylamine, hippurate, and phenyacetylglutamine.45 Another study showed that urinary levels of 3-(3-hydroxyphenyl)-3-hydroxypropionic Inhibitors,research,lifescience,medical acid (HPHPA) are higher in children with autism compared with neurotypical controls.44 One potential source of this compound is the conversion of phenylalanine from the diet to m-tyrosine and then to 3-hydroxyphenyl-propionic acid by microbial enzymes, followed by conversion to HPHPA by human enzymes.44 m-Tyrosine induces a characteristic behavioral symptom in rats that includes stereotypical Astemizole behavior, hyperactivity, and hyper-reactivity,55 indicating that this compound may be specifically contributing towards autistic behaviors. A microbial origin for HPHPA is supported by its decrease in urine after patients were treated for Clostridial infections with metronidazole, an antibacterial agent with specificity toward anaerobic bacteria.44 Some species within the Clostridiales are known to produce phenylpropionic acid and/or monohydroxyphenylpropionic acid, which are very closely related biochemically to m-tyrosine and HPHPA.

140 Most

of the medications used commonly in neurorehabilitative practices are mechanistically pleotropic.The several possible neurochemical effects of a given medication in the neurometabolic and neurochemical milieu into which it is introduced therefore are necessary considerations during treatment selection and will guide treatment response expectations. For example, early post-injury administration of uncompetitive NMDA receptor antagonists such as amantadine (or, perhaps, memantinc) may attenuate the adverse effects of early glutamate excesses and facilitate progression from posttraumatic Inhibitors,research,lifescience,medical coma to higher stages of PTE. In the subacute or late post-injury period, the clinical benefits of amantadine141 on post-traumatic disorders of consciousness (ie, vegetative or minimally conscious states after severe TBI) may reflect its NMDA receptor function-stabilizing Inhibitors,research,lifescience,medical properties, indirect facilitation of dopamine release by NMDA antagonism, other synapse-related effects on dopamine neurotransmission, or some combinations of these pharmacologic effects. When this same agent is used to treat the cognitive Inhibitors,research,lifescience,medical and other neuropsychiatric manifestations of the post-traumatic dysexecutive syndrome, especially after mild or moderate TBI,

the beneficial effects of amantadine most likely reflect enhanced frontal function via indirect augmentation of cerebral dopaminergic activity.36,119,120 Zolpidem provides another example

of the differential neuropsychiatric Inhibitors,research,lifescience,medical effects on a specific cognitive target, based on the context (ie, initial injury severity, stage of PTE, time Inhibitors,research,lifescience,medical post-injury) in which it is administered. Zolpidem binds to GABAA receptors and thereby potentiates the effect, of G ABA, the principal inhibitory neurotransmitter in the central nervous system. Among persons with relatively intact arousal systems and minimal disturbances in other modulator}’ neurotransmitter systems (ie, persons in post-traumatic dysexecutive syndrome stage of PTE. during the subacute or late postinjury periods following mild TBI), Zolpidem is likely to impair arousal – hence its common use as an agent, with which to treat insomnia. However, when administered to individuals with severely Thalidomide altered arousal and attentional systems in the subacute or late post-injury period following severe TBI (ie, persons with persistent post traumatic disorders of consciousness), Zolpidem may reciprocally disinhibit arousal systems among persons in the lower stages of PTE.141,142 Whether this reflects a direct of U0126 supplier effect of its action at GABAA receptors or a secondary effect, of those actions on the function of other modulatory neurotransmitter systems remains uncertain.

110-112 This effect has been attributed to blunting the stimulatory effect of alcohol, enhancing the sedative effect, and/or decreased levels of reinforcement from alcohol. Conclusions The use of the current DSM-IV classification for alcohol use disorders has proven impractical in the pursuit

of identifying predisposing genetic and environmental risk factors for the complex phenotype of dependence on alcohol. This can be attributed to the fact that many researchers have used DSM-IV criteria to arrive at binary classifications based on a range of symptoms and, thus, do not capture the heterogeneity of the disorder. Inhibitors,research,lifescience,medical The ability to study well the multiple factors that contribute to the development of “alcoholism” will depend on the creation of more homogeneous subgroups by use of endophenotypes. This can be achieved through the development of new classification schemes based on genetic/biological, physiological, and behavioral endophenotypes. Future research in the area of alcohol use disorders will continue to improve phenotypic definitions Inhibitors,research,lifescience,medical and ultimately contribute to the disentanglement and elucidation of the etiology of the various components that contribute Inhibitors,research,lifescience,medical to the multifaceted and complex syndromes currently Small molecule library research buy encompassed by the DSM-IV, the International Classification of Mental and Behavioral Disorders (ICD-10), and the lay public perceptions

of alcohol use disorders. Notes Research endeavors Inhibitors,research,lifescience,medical of the authors are supported by NIAAA and the Banbury Fund.
Epidemiological studies reveal the importance of family function and early life events as predictors of health in adulthood.1 As adults, victims of childhood physical

or sexual abuse, emotional neglect, family conflict, and conditions of harsh, inconsistent discipline are at considerably Inhibitors,research,lifescience,medical greater risk for mental illness, as well as for obesity, diabetes, and heart disease.2-17 These difficult conditions, in part, define the developmental origin of mental illness in adolescence and adult life. “Stress diathesis” models suggest that adversity in early life alters the development of neural and endocrine systems in a manner that predisposes individuals to disease in adulthood. The relation between the quality of the early environment and health 3-mercaptopyruvate sulfurtransferase in adulthood appears to be mediated by parental influences on the development of neural systems that underlie the expression of behavioral and endocrine responses to stress.1,18-22 Adversity or decreased quality of parental investment increases the magnitude of emotional, autonomic, and hypothalamicpituitary-adrenal (HPA) responses to stress in adulthood. These models are constructed on two principal assumptions: (i) prolonged activation of neural and hormonal responses to stress can promote illness; (ii) early environmental events influence the development of these responses. There is strong evidence in favor of both ideas.

As observed with connexin 40 mutants, the aberrant form of connexin 43 abolished gap junction formation in the presence of both wild-type connexin 40 and 43,

consistent with dominant- and transdominant negative loss-of-function effects, respectively. Collectively, these findings provide compelling evidence that somatic or atrial-specific genetic defects within both Inhibitors,research,lifescience,medical connexin 40 and 43 predispose to the development of sporadic, lone AF. The presence of genetic mosaicism in the context of these loss-of-function connexin mutations is likely critical for their role in promoting arrhythmogenesis within atrial tissue. A predisposition to the chaotic electrical reentry circuits characterizing AF will likely be greater in the presence of an arrhythmogenic substrate that exhibits substantial Lapatinib price regional variability in conduction velocity. Furthermore, the general notion that regional variability of cardiac electrical properties is proarrhythmic provides support for a potential broader role of genetic mosaicism in the pathogenesis of AF. It should

Inhibitors,research,lifescience,medical be noted, however, that genetic mosaicism Inhibitors,research,lifescience,medical does not appear to be a prerequisite for the development of AF in the presence of connexin mutations. Since our original findings, multiple reports have emerged in the literature implicating connexin 40 mutations in cases of familial AF.41, 42 Mechanistic Subtype of AF 4: Cellular Hyperexcitability Initial studies had implicated loss-of-function SCN5A mutations in the development of AF, but the arrhythmogenic potential of gain-of-function SCN5A mutations Inhibitors,research,lifescience,medical had also been well documented in long QT syndrome type 3.43 Long QT syndrome type 3 develops secondary

to an SCN5A gain-of-function effect that prolongs cardiac repolarization through an increased late sodium current.44 The importance of SCN5A gain-of-function mutations in AF pathogenesis Inhibitors,research,lifescience,medical was confirmed after investigations involving a four-generation Japanese family with an autosomal dominant form of AF that carried a novel SCN5A Met1875Thr mutation.45 The novel variant exhibited perfect genotype-phenotype segregation within the family, consistent with its being fully penetrant, and was also absent from 210 ethnically Terminal deoxynucleotidyl transferase matched controls. The proband was noted to have increased right atrial excitability during radiofrequency catheter ablation for AF. Functional analysis of Met1875Thr revealed a pronounced depolarizing shift in the midpoint of steady-state inactivation consistent with a gain-of-function effect. No increased late sodium current was observed, accounting for the presence of normal QT intervals within affected individuals. A second study from our group involving a mother and son with lone AF identified a Lys1493Arg mutation involving a highly conserved residue within the DIII-IV linker located 6 amino acids downstream from the fast inactivation motif of sodium channels.

strategy and choice behavior that is disadvantageous in the long run) compared with the PRLT, and, therefore, we have chosen to discuss only the IGT and the two-choice prediction task in this section. Idelalisib datasheet Although the PRLT also comprises a decision making or choice component, the PRLT is not seen as a gambling

task but a task measuring flexibility of learned behavior based Inhibitors,research,lifescience,medical on contingencies without the strategic element of long-term versus short-term advantages. Memory Immediate memory (and working memory: WM), is often assessed with the Wechsler Adult Intelligence Scale (WAIS) Digit Span or Memory Span task, requiring the person to remember a string of digits, letters or words. The N-back task is a continuous WM task which requires subjects to indicate whether the current letter matches the one from n (usually 1–3) steps earlier (Kirchner 1958). Delayed memory is addressed in the immediate memory task/delayed memory task (IMT/DMT), a task similar to the N-back task but Inhibitors,research,lifescience,medical with additional options (Dougherty et al. 2002), such as delaying the recognition phase up to several minutes. While these tasks mainly differ in the delay of

the recognition phase, also the memory load differs in several tasks. For Inhibitors,research,lifescience,medical example, in the N-back task, working memory load can be increased by incorporating more steps back to be remembered in a short-time period, while the IMT/DMT can increase working memory load during a longer time period Inhibitors,research,lifescience,medical up to several minutes according to the task’s design. Memory span tasks can also be made more challenging (increasing working memory load), that is, by instructing the individual to name the memory sets backwards. The WAIS digit span is similar to other memory span tasks, but is part Inhibitors,research,lifescience,medical of the more comprehensive full WAIS measuring both verbal intelligence quotient (IQ) and performance IQ. During a WM span task, male smokers performed worse than nonsmoking male HCs (Greenstein and Kassel 2009). Ecstasy users performed worse than HCs on a verbal DMT, and total ecstasy use was negatively associated with memory

performance (Schilt et al. 2008). On a delayed memory recognition task, administration of a nicotine patch improved performance accuracy in nonsmokers (Froeliger et al. 2009). With regard to acute abstinence effects, in male smokers, memory performance declined across a 60-min test period, whereas aspects of next calculation and association tasks improved over time (Sakurai and Kanazawa 2002). Cognitive flexibility, attention, and planning Attention is a complex process that can be divided in different aspects. For instance, sustained attention is the ability to maintain attention for a longer period on a certain task which can be measured using a sustained attention task, whereas divided attention is the ability to shift attention between different task demands.

To address this issue, we then examined OPC proliferation using BrdU labeling. The percentage of BrdU+ cells was significantly increased in cultures exposed to ACDM (Fig. ​(Fig.2B),2B), but not MCDM (Fig. ​(Fig.2C)2C) or the control (Fig. ​(Fig.2A).2A). To further identify the specific factors that mediate ACDM-enhanced OPC proliferation,

the activity of PDGFaa, bFGF, and IGF-1, three major cytokines known to be secreted by astrocytes, were blocked using neutralizing antibodies. The data showed that blocking PDGFaa and bFGF, but not IGF-1, significantly reduced the number of BrdU+ cells in ACDM-exposed Inhibitors,research,lifescience,medical cultures (Fig. ​(Fig.22E). Figure 2 ACDM, but not MCDM, promotes OPC proliferation. After being exposed to the control or the conditioned medium for 48 h, OPC proliferation was assessed Inhibitors,research,lifescience,medical by BrdU labeling. (A) Representative photographs show that the number of BrdU+ cells, which was minimal … Although ACDM significantly promoted OPC proliferation, the number of BrdU+ cells only accounted for 10% of total cells (Fig. ​(Fig.2B),2B), suggesting

that newly generated cells only partially contributed to the higher rate of OL survival noted in ACDM- versus MCDM-treated cultures. By assessing the number of both apoptotic cells (pyknotic nuclei) and total cells (pyknotic nuclei and intact nuclei combined) at 8 days of treatment, it showed Inhibitors,research,lifescience,medical that the percentage of degenerated cells was significantly lower in ACDM-treated (22.2%) compared with MCDM-treated Inhibitors,research,lifescience,medical cultures (41.9%), while the total number of cells was 11.5% higher in ACDM versus MCDM-treated cultures. MCDM, but not ACDM, enhances OL differentiation OLs maintained in MCDM displayed profound morphological changes, which

were readily discernable under the invert microscopy as early as 24 h. The most notable change was the development of comprehensive process network (Figs. ​(Figs.1A1A and ​and3).3). To better characterize the effects of the conditioned medium on OL differentiation, Inhibitors,research,lifescience,medical a panel of OL developmental markers with distinct immunocytochemical labeling patterns was used (O4 and MBP label both somata and processes of immature OLs and mature OLs, respectively; APC labels only somata of mature OLs; and Rip labels fine processes of both immature and mature OLs). As shown in Figure ​Figure3,3, MCDM strongly this website accelerated OL differentiation as evidenced by Ketanserin higher percentages of APC+ mature OLs (Fig. ​(Fig.3F)3F) with concomitant lower percentages of O4+ OPCs (Fig. ​(Fig.3C)3C) in 8-day cultures. In contrast, although ACDM also significantly increased APC+ mature OLs (Fig. ​(Fig.3E)3E) when compared to the control, the effect was much weaker than that of MCDM (14.7 ± 1.6 vs. 75.6 ± 3.1, P < 0.01). In fact, cells maintained in ACDM remained primarily as undifferentiated O4+ immature OLs (Fig. ​(Fig.