Mitochondrial genetics and

cardiological disorders The human mtDNA is a 16,569-bp, double-stranded, circular molecule containing 37 genes, 24 of which participate in the translation mechanism (2 rRNA’s – 22 tRNA´s). The 13 remaining genes left are responsible for the synthesis of respiratory chain subunits. Hence, among the approximately 900 genes that participate in the function of the organelle, only a few are localized in the mtDNA, whereas the remainder are in the nDNA. This explains why about 50% of adults and 80-90% of children, suspected to have a mitochondrial disease on the basis of biochemical and/or morphological features, #Na K-ATPase activity keyword# remain Inhibitors,research,lifescience,medical genetically undiagnosed. Indeed, it is reasonable to believe that most mitochondrial diseases are caused by undiscovered nuclear genes (12-14). On the other hand, mtDNA mutations, which were studied in greater details, obey to different genetic rules than those applied to “mendelian” disorders (15). First, mtDNA is maternally inherited as sperm mitochondria’s are eliminated early in embryogenesis. Hence, mtDNA

Inhibitors,research,lifescience,medical will only be transmitted through the maternal line. Second, there are multiple copies of mtDNA in each cell: homoplasmy refers to the situation in which all mtDNA copies are identical. If two or more sequence variants exist in a cell or individual, that condition Inhibitors,research,lifescience,medical is referred to as heteroplasmy. If deleteriously mutant (i.e, pathogenic) and normal mtDNA coexist in the same cell, the respiratory chain function will not be impaired

as long as there is sufficient normal mtDNA to overcome the effects of mutant DNA. If, however, the ratio of mutant to normal mtDNA exceeds a certain critical threshold, then the respiratory chain function will be impaired. The threshold at which symptoms will manifest depends on the tissue Inhibitors,research,lifescience,medical involved. Skeletal muscle (especially extraocular muscles) brain, heart, retina, renal tubular cells, and auditory cells of the organ of Corti are the most common tissues affected. Third, mitotic segregation of the multiple existing copies of mtDNA explains not why the level of mutant mtDNA can change during life (16); this may depend on the stage of embryonic development in which the original mutation occurs. Point mutations vs large rearrangements As a general rule, mtDNA can harbour two different types of genetic variants, point mutations or large-scale rearrangements, which can involve deletions, duplications, or both together. Point mutations are commonly maternally inherited and they may differ from non pathogenic polymorphisms since a single change of a nucleotide base (e.g. A to G in position 3243 commonly for MELAS) (17) produces subsequently modifications in the corresponding product leading to defects in protein conformation.

The past medical history was remarkable for significant coronary artery disease, diabetes mellitus, hyperlipidemia, hypertension, paroxysomal

atrial fibrillation, and scoliosis. The patient was on multiple medications for hypertension, diabetes mellitus, and high cholesterol. There was no family history of prostate or breast cancer. The patient had a 50 pack-year smoking history, which he discontinued in 2003. On physical examination, there was no costovertebral angle tenderness bilaterally and the abdomen was soft, nontender, and nondistended, with normal bowel sounds. The testes were bilaterally descended without masses. Inhibitors,research,lifescience,medical Both epididymides and vasa were unremarkable. There were no mTOR inhibitor inguinal hernias. There was a 1-cm nodule occupying the right

lateral portion of the prostate base that was confined to the gland. A preoperative MRI of the prostate before and after intravenous gadolinium contrast injection including dynamic imaging of the inguinal areas during Valsalva was performed Inhibitors,research,lifescience,medical to stage the prostate cancer prior to radical prostatectomy and to identify occult inguinal hernias. On MRI, the prostate was small, with a calculated volume of 14 cc. There were nonspecific low T2 signal areas throughout the peripheral zone without focal mass and no evidence of gross extracapsular extension, seminal vesicle Inhibitors,research,lifescience,medical invasion, or pelvic lymphadenopathy. A left dilated ectopic ureter inserting into the prostatic urethra was incidentally noted (Figure 1). Figure 1 Axial (A, B), sagittal (C, D), and coronal (E, F) T2-weighted images show ectopic insertion of a dilated left ureter inserting into the prostatic urethra. *Urinary bladder. A MAG-3 renogram (Figure 2) demonstrated normal right renal function. On the left, there was prompt uptake

and excretion Inhibitors,research,lifescience,medical of the isotope in both the upper and lower pole moieties. Figure 2 Renogram Inhibitors,research,lifescience,medical with injection of mercaptoacetyltriglycine (MAG-3) without lasix of the kidneys. The time to peak was 4 minutes bilaterally. The clearance half-time was 17.9 minutes on the left and 14.9 minutes on the right. The split function was 40.6% for … A CT urogram with reformats was obtained to better visualize the anatomy of the left duplicated system and associated upper pole ectopic ureter (Figure 3). CT showed a partial duplication of the right pelviocalyceal system with a single ureter emptying directly into the bladder. There was complete duplication of the left collecting system Tolmetin and ureter. The lower pole ureter was not dilated and drained orthotopically into the bladder. The upper pole ureter was dilated distally and terminated in the prostatic urethra. Otherwise, the bladder and prostate were morphologically normal. Figure 3 Three-dimensional volume rendered (A) and maximum intensity projection images obtained from the computed tomography urogram. The images showed partial duplication of the right pelviocalyceal system with a single right ureter and complete duplication of …

Figure 3 The bottom-up pathway

of the hippocampus-VTA loop mediates positive place reinforcement learning following conditioning the VTA. (A) Baseline place preference is defined by the amount of time per session prior to the commencement of IC-CPP. Rats were … In rats previously trained with intra-VTA-METH CPP, intra-VHC-METH produced positive place reinforcement learning 24 h following conditioning After we finished our assessments on intra-VTA-METH-induced CPP learning, the same groups Inhibitors,research,lifescience,medical of rats from “METH produced positive place learning following conditioning the VTA” were conditioned with either METH or Ringer’s intra-VHC, for the first time (refer Fig. 1B). There was a significant interaction between treatments (Base [n = 11], Ringer’s [n = 9], METH [n = 10]) and test (Test 4, Test 5, Test 6) (F [6, 49] = 3.39, P < 0.01). Following the first-time mTOR inhibitor intra-VHC exposure, the Inhibitors,research,lifescience,medical two groups did not statistically differ from one another, but both groups showed significant positive CPP toward the drug-paired chambers compared to the baseline condition

(P < 0.005). The time deviation for the Inhibitors,research,lifescience,medical METH-paired chambers following the second conditioning session was significantly reduced to a negative value below baseline (P < 0.005), however, there were no significant differences between METH-paired and Ringer's-paired groups on time deviation from the baseline condition (P = 0.67). To our surprise, 24 h following conditioning, METH rats, but not Ringer's rats, spent a significantly greater amount of time in METH-paired chambers compared

to both the Ringer’s group (P < 0.05) and the baseline condition (P < 0.05) (Fig. 4B–D). In addition, METH groups spent a significantly more time in METH-paired Inhibitors,research,lifescience,medical chambers compared to Ringer's-paired chambers (P < 0.01). Figure 4 The bottom-up pathway of the hippocampus-VTA loop mediates positive place reinforcement learning Inhibitors,research,lifescience,medical following conditioning the VHC. (A and B) Total amount of time spent (30 min/session/day); (A) in the Ringer's-paired, and (B) in the METH-paired chambers ... In rats previously trained with Mephenoxalone intra-VTA-METH followed by intra-VHC METH, intra-NAc-METH also produced an augmented positive place reinforcement learning 24 h following conditioning The NAc is highly implicated in the expression (or maintenance phase) of addictive behaviors associated with substances of abuse including METH (Rodriguez et al. 2008). Thus, to see the effect on the maintenance of IC-METH-CPP learning, we continued the experiment by finally conditioning the NAc. Therefore, the same rats from “In rats previously trained with intra-VTA-METH CPP, intra-VHC-METH produced positive place reinforcement learning 24 h following conditioning” were conditioned and tested with either METH or Ringer’s intra-NAc, for the first time (Fig. 1B).

Largely due to the influence of Klein’s

hypothesis that agoraphobia is a conditioned avoidance response to the aversive stimulus of spontaneous panic attacks, the diagnostic view of agoraphobia changed considerably in DSM-III-R, in which PD is viewed as primary, with or without secondary development of agoraphobia. An important factor in this change was the observation by Klein3 and others that, in clinical settings, agoraphobia rarely occurs without preceding spontaneous panic attacks or limited symptom Inhibitors,research,lifescience,medical attacks. However, Marks and other investigators57 have questioned the temporal precedence and causal role of panic attacks in the development of agoraphobia. Table VIII. Comorbidity of panic disorder (PD) with lifetime agoraphobia. ECA, Epidemiological Catchment Area survey; NCS, National Comorbidity Survey. The large differences selleck products between clinic and community studies in estimates of the relative prevalence of agoraphobia with and without panic attacks contribute to the controversy. Inhibitors,research,lifescience,medical Population-based surveys have identified a substantial number of subjects with agoraphobia and no history of panic attacks. For the most part, subjects in these surveys were interviewed by laypersons using the DIS. In contrast, clinic-based studies, using less structured interviews administered by clinicians, almost invariably found Inhibitors,research,lifescience,medical much lower rates of agoraphobia

without panic. Several explanations for this discrepancy have been suggested. One is that treated samples of persons with any illness have higher rates of comorbidity than untreated samples. An alternative explanation is that population studies may have overestimated Inhibitors,research,lifescience,medical the rate of agoraphobia without PD. In a reanalysis of the ECA data on agoraphobia without panic, 22 community cases of agoraphobia without panic were clinically reappraised and only a single case of probable agoraphobia without panic was Inhibitors,research,lifescience,medical found.28 The diagnostic reappraisal found that 19 (87%) of the cases had simple or SPs rather than agoraphobia, or no DSM-III phobia at all. The reappraisal also identified 6 cases

of PD, panic attacks, or limited symptom attacks that had been missed by the DIS interview. The authors concluded that community studies using the DIS may have overestimated the prevalence of agoraphobia without panic attacks in also the community. An initial analysis of the NCS data found that only about one-third of NCS agoraphobics reported a history of panic attack. More detailed analyses of the NCS data are under way to determine whether agoraphobia without panic is in fact as common as the initial analyses suggest. Social phobia Diagnosis SP is a common disorder associated with significant psychosocial impairment, representing a substantial public health problem, largely determined by high prevalence and lifelong chronicity.

Immunohistochemistry Serial cryosections (4 µm) of each muscle biopsy were air-dried and fixed with acetone for 15 minutes. Unspecific binding was reduced by 30 min incubation with 5% bovine serum albumin (BSA) and 3%

goat serum (Jackson ImmunoResearch Laboratories, West Grove, PA, USA) in PBS. All primary and secondary reagents were CO-1686 diluted in 1% BSA. Staining with a single antibody Inhibitors,research,lifescience,medical was performed using an alkaline phosphatase/anti-alkaline phosphatase technique (Dako, Hamburg, Germany). Neu-Fuchsin was used as chromogen. The first antibody was omitted in controls. Sections were counterstained with haematoxylin, dehydrated and mounted in Eukitt (Merck, Darmstadt, Germany). Conventional double-labelling immunohistochemistry For detection of IFN-γ and 25F9, a secondary goat-anti mouse-alkaline phosphatase Inhibitors,research,lifescience,medical antibody (1:500, Dako) for 60 min was used. Subsequently, a biotinylated 25F9 (1:50, biotinylated with DakoARkTM-Kit, Hamburg, Germany) was applied for 60 min, followed by a streptavidin/HRP conjugate (DakoARKTM-Kit) for another 30 min. Sections were developed using the chromogens DAB and Neu-Fuchsin. Immunofluorescent double Inhibitors,research,lifescience,medical labelling immunohistochemistry For immunofluorescent double-labelling, sections were sequentially

stained for iNOS or TGF-β and an Alexa488 goat anti-rabbit IgG secondary antibody (Molecular Probes/Invitrogen, Karlsruhe, Germany). Subsequent staining for 25F9 was visualized by Inhibitors,research,lifescience,medical an Alexa594 goat anti-mouse IgG secondary antibody (Molecular Probes/Invitrogen). Nuclear counterstaining was performed by DAPI, followed by mounting in Fluoromount G (Electron Microscopy Sciences, Hatfield, PA, USA). Immunofluorescent

microscopy and digital photography was performed on a Zeiss Axiophot microscope (Zeiss, Gttingen, Germany), using appropriate filtres for green (488 nm), red Inhibitors,research,lifescience,medical (594 nm) and blue (350 nm) fluorescence and a cooled CCD digital camera (Retiga 1300, Qimaging, Burnaby, BC, Canada) using the Qcapture software. Results Expression of IFN-γ, iNOS, and TGF-β and co-staining with 25F9-positive late-activated macrophages in patients with PM and DM. IFN-γ expression In PM and DM, IFN-γ was abundantly expressed in inflammatory cells located primarily in the endomysium. IFN-γ expression, in PM, was detected not only very around necrotic or inflamed muscle fibres but also around muscle fibres without cellular infiltrates. IFN-γ expression in DM was present in the endomysium and perivascular infiltrates (Figs. ​(Figs.1A,1A, ​A,2A).2A). Double-labelling studies showed that macrophages expressing the late-activation marker 25F9 did not stain positive for IFN-γ in PM (Fig. ​(Fig.3A)3A) or in DM. Figure 1A-C Serial staining for IFN-γ, iNOS, and TGF-β in representative muscle biopsy of 42-year-old patient with PM.

4,6,7 This issue is further aggravated by the 1- to 2-year waiting list for entering a presurgical evaluation program in the majority of epilepsy surgery centers. Several reasons underlie the above situation, including the patients’ and physicians’ legitimate fear of a postoperative permanent neurological deficit, the frequently insidious IBET151 course of chronic epilepsy,8 the relatively low yield of long-term postoperative seizure freedom (~ 60% after 10 years of follow-up),9 the paucity of randomized control trials (RCTs) demonstrating the efficacy of surgical therapy over antiepileptic drugs (AEDs),10 the complexity and heterogeneity Inhibitors,research,lifescience,medical of surgical treatments,

and the limited resources dedicated to the presurgical evaluation of epilepsy patients. Some of these reasons can now be challenged. For instance, major safety progress has been made in the field of neurosurgery, with a risk of unexpected vascular or infectious complications Inhibitors,research,lifescience,medical resulting in a residual disabling neurological impairment of about 1% in experienced epilepsy surgery groups.2,11 Thus,

the risk of seizurerelated death or serious injury in drug-resistant patients refusing epilepsy surgery (about 1 % per year), is significantly higher than the major morbidity/mortality associated with surgical treatment (about l%in total). The suboptimal Inhibitors,research,lifescience,medical yield of postoperative long-term seizure freedom must also be balanced with the much worse figures reported in patients who have not been operated on, only 5% to 14% of whom will achieve seizure remission.12,13 Altogether, the available data in the literature strongly suggest that epilepsy surgery is Inhibitors,research,lifescience,medical significantly more efficacious than medical treatment. Eligibility criteria for presurgical evaluation and epilepsy surgery Patient selection for epilepsy surgery is a two-step procedure that first aims to identify Inhibitors,research,lifescience,medical potential surgical candidates who should benefit from a presurgical evaluation, and then to determine in each assessed individual whether

the risk:benefit ratio for surgery is acceptable. Three main criteria must be fulfilled to enter the first next step: (i) the patient (or his or her parents for young children and patients with intellectual impairment) needs to understand the objective of the presurgical evaluation and to agree on the possibility of a surgical treatment; (ii) the patient should suffer from disabling seizures despite appropriate medical therapy; and (iii) available imaging and electroclinical data should be consistent with the possibility of a surgically remediable epileptic syndrome. The first criterion is minor, but should not be overlooked, since it often represents a limiting factor in patients who would otherwise be considered good surgical candidates. The second criterion relies on the definition of disability and drug resistance.

The baseline demographic characteristics for the individual studies and the pooled population are described in Table ​Table11. Table 1 Baseline demographic characteristics

Outcomes The CAPS-SX17 was the primary outcome measure for both studies. The CAPS-SX17 is a rating scale based on the 17 PTSD symptoms Inhibitors,research,lifescience,medical described in DSM-IV (Table ​(Table2),2), which includes three clusters or subscales (i.e., reexperiencing, avoidance/numbing, and hyperarousal). Table 2 DSM-IV/CAPS-SX17 PTSD symptom clusters (the prespecified three-factor structure) Statistical analysis Factor analyses These factor analyses were performed using baseline data collected prior to treatment administration, which allowed for the pooling of the venlafaxine ER and placebo treatment arms of both studies. Inhibitors,research,lifescience,medical Additionally, separate analyses of each individual study were conducted as a means of cross-validation. An initial confirmatory factor analysis (CFA) was performed using the prespecified three-factor structure

described in the DSM-IV to determine whether the current data fit this structure. If the data did not fit, an exploratory factor analysis (EFA) was planned to identify symptoms that cluster in this population and to assess how these factors respond Inhibitors,research,lifescience,medical to treatment. The CFA was performed using a maximum likelihood factor extraction method for normally distributed data and a weighted least-squares Inhibitors,research,lifescience,medical factor extraction method for categorical data; two methods were used to see if similar factors were extracted with both methods. These CFA models used Hu and Bentler’s (1999) recommendation of a combination of two goodness-of-fit

indexes (Hu and Bentler 1999). This combination included a noncentrality-based index such as a root mean square error of Vemurafenib cell line approximation (RMSEA) to indicate the amount of unexplained variance with a criteria of <0.60, and a relative Inhibitors,research,lifescience,medical fit index, such as Bentler–Bonett Non-normed Index that has a penalty for adding parameters with a criteria of >0.90 for acceptable fit. The EFA was performed using a TCL polychoric correlation covariance matrix; a technique for estimating correlations among theorized normally distributed continuous latent variables from observed ordinal variables. A sensitivity analysis was conducted that used the Pearson correlation matrix. The maximum likelihood extraction method was used to extract the factors, and an oblique, promax factor rotation method was used to allow for correlated factors. The maximum likelihood factor extraction method, which provides statistical testing (i.e., goodness of fit for the model, significance testing of factor loadings), is best for relatively normally distributed data (Fabrigar et al. 1997).

The iatrogenic nature of supersensitivity psychosis raises questions about the use of antipsychotic medications as they may ultimately cause adaptive changes in the brain that lead to treatment failure. Caution should be exercised before increasing doses in relapsing patients. It is suggested that further research into prescribing regimes is required, including alternative dosing strategies, switching Inhibitors,research,lifescience,medical to antipsychotics with a lower affinity for dopamine D2 receptors and augmentation with novel agents. As the main providers of community mental healthcare, CPNs occupy a key position in monitoring and supporting KU-57788 supplier people with psychosis. An awareness that relapses can occur in medication-compliant

patients will inform assessments of mental health and avoid mistrust occurring in the nurse–patient relationship. Furthermore, as AIMs and life events may provoke a breakthrough of psychotic Inhibitors,research,lifescience,medical symptoms, mental health nurses need training

in recognizing side effects and how to assess for life events. Appendix 1 Supersensitivity psychosis checklist Supersensitivity psychosis syndrome recognition criteria Criterion Description A International Classification Inhibitors,research,lifescience,medical of Diseases (ICD-10) diagnosis of schizophrenia or schizoaffective psychosis. Treated > 1 year with antipsychotic medication (excludes clozapine and quetiapine). Compliant with antipsychotic medication. B Emergence or exacerbation of positive psychotic symptoms from the following list: hallucinations, including nonverbal

auditory, verbal Inhibitors,research,lifescience,medical auditory, functional hallucinations, visual hallucinations and olfactory hallucinations; delusions, including delusions of misinterpretation, misidentification, persecution, conspiracy, religious delusions and delusions of grandiose abilities; thought disorder, including thoughts being read, loud thoughts, thought echo, thought broadcast and thought insertion. C Abnormal Inhibitors,research,lifescience,medical involuntary movements, which may include movements of the tongue, face, jaw, lips and trunk, also purposeless jerky or writhing movements of limbs; excludes Parkinsonian tremor, rigidity and associated akathesia. D Life events are likely to be absent or of a minor degree of threat. E The symptoms of criteria B and C are clinically significant identified by the fact that they cause interference of social and/or occupational functioning. 4-Aminobutyrate aminotransferase F The symptoms are not due to any organic brain injury, alcohol consumption acceptable if within British Medical Association guidelines (alcohol guidelines for sensible drinking 1995, 14 units per week for women, 21 units per week for men); there should be no significant illicit drug misuse. Footnotes This work was supported by the Department of Health UK R&D Training Fellowship (grant number RDO/33/94) to Paul Fallon. The authors declare no conflicts of interest in preparing this article.

1,2 In fact, the World Health Organization identified OCD among the top 20 causes of years of life lived with disability for 15- to 44-year-olds.3 Although generally longitudinally stable, OCD is known for its substantial heterogeneity, as symptom presentations and comorbidity patterns can vary markedly in different individuals. Moreover, a number of other psychiatric and neurologic disorders have similar phenomenological features, can Inhibitors,research,lifescience,medical be comorbid with OCD, or are sometimes even conceptualized as uncommon presentations of OCD. These include the obsessive preoccupations and repetitive behaviors found in body dysmorphic disorder, hypochondriasis, Tourette

syndrome, Parkinson’s disease, Inhibitors,research,lifescience,medical catatonia, autism, and in some individuals with eating disorders (eg, anorexia nervosa).4-10 These heterogeneous facets of the disorder have led to a search for OCD subtypes that might be associated with different etiologies or treatment responses. Ruminative, obsessional, preoccupying mental agonies coupled with perseverative, ritualized compulsionresembling behaviors have been depicted in biblical

documents as well Inhibitors,research,lifescience,medical as Greek and Selleckchem GSK1363089 Shakespearian tragedies. In modern nosology, a number of different approaches have been suggested to characterize this syndrome, yet the question of how best to categorize OCD subgroups remains under debate in 2010. Currently, the Diagnostic and Statistical Inhibitors,research,lifescience,medical Manual of Mental Disorders (DSM-IV-TR) of the American Psychiatric Association, classifies OCD as an anxiety disorder. There have, however, been questions raised about this categorization

on the basis of some phenomenological differences between OCD and the other anxiety disorders. As such, suggestions have been made that, in the forthcoming 2012 DSM-5, OCD should be removed from its position as one of the six anxiety disorders – a reformulation Inhibitors,research,lifescience,medical still under debate. One solution under discussion is that OCD should constitute an independent entity in DSM-5 (ie, remain outside of any larger grouping), congruent with its designation as such in the current international diagnostic manual, ICD-10 (International Statistical Classification of Diseases and Related Health Problems).11-14 An alternative suggestion would group OCD and related disorders into a new Obsessive-Compulsive Thymidine kinase Spectrum Disorders (OCSD) category. The concept of an OCSD classification was first postulated over a decade ago.15,16 Later, the original OCSD concept was extended with the proposal that OCD and other compulsive disorders may lie along a larger continuum of corelated compulsive-impulsive disorders.15 Disorders hypothesized at the impulsive end of this spectrum continuum include pathologic gambling, nonparaphilic compulsive sexual activity, and others.

4.3. Multi-Dimensional MS-Based Shotgun ABT-199 lipidomics The multi-dimensional MS (MDMS)-based shotgun lipidomics platform maximally exploits the unique chemistries inherent in distinct lipid classes to identify and quantify individual lipid species after direct infusion [4,10,48]. For example, MDMS-based

shotgun lipidomics utilizes a multiplexed extraction approach that exploits differential hydrophobicity or differential chemical stability under acidic or basic conditions to separate and/or enrich differential lipid classes by liquid/liquid partitioning or by multiplexed chemistries [10]. MDMS-based shotgun lipidomics also exploits the differential charge Inhibitors,research,lifescience,medical properties to achieve selective ionization of differential Inhibitors,research,lifescience,medical lipid classes under multiplexed infusion conditions that allow intrasource separation of lipids in different classes or categories [49]. In addition, MDMS-based shotgun lipidomics exploits the uniqueness of individual lipid classes to identify and quantify lipids in specific lipid

classes. Examples include quantification Inhibitors,research,lifescience,medical of cardiolipins through use of the unique doubly-charged molecular ions resulting from the presence of two phosphate moieties present in cardiolipin resulting in M + 0.5 isotopologue patterns [50]; identification and quantification of phosphoethanolamine-containing lipid species Inhibitors,research,lifescience,medical by the specific derivatization of primary amine with fluorenylmethoxylcarbonyl (Fmoc) chloride [51]. MDMS-based shotgun lipidomics utilizes the principle of building block analysis for identification of individual lipid species by employing two powerful MS/MS techniques Inhibitors,research,lifescience,medical (i.e., PIS and NLS)

in a mass-ramp fashion [10]. Specifically, PIS or NLS of the fragment ion(s) resulting from the head group or the neutral loss of the head group building block identifies the lipid class of interest, and PIS or NLS of fatty acyl building blocks identifies the individual Parvulin lipid species in the class. The class-specific diagnostic ions are also exploited for lipid quantification. In contrast to the other two shotgun lipidomics platforms, MDMS-based shotgun lipidomics quantifies the identified individual lipid species using a two-step procedure that incorporates not only exogenously added, pre-selected internal standards, but also endogenous lipid species that are quantifiable accurately in a full MS survey scan. Specifically, in the first step, the platform employs a full MS scan acquired after intrasource separation and the pre-selected internal standard of the class of interest for quantification of lipid species that are abundant and not overlapped with lipid species from other classes.