The 2018 AACC/SYCL PhD Clinical Chemist Compensation Survey.

BACKGROUND: Doctoral level board-certified clinical chemists play an invaluable role in many facets of laboratory medicine and healthcare. However, information concerning their total compensation is sparse. CONTENT: A confidential self-reported compensation survey was conducted by the American Association for Clinical Chemistry's Society for Young Clinical Laboratorians (AACC SYCL) Core Committee from April 1 to April 17, 2018. Respondents provided information on geographic location, employment sector, gender, and years of experience to account for the influence of these variables on compensation. There were 199 respondents in total from the United States and Canada, however, only respondents employed in the United States with an earned doctoral degree and certification by the American Board of Clinical Chemistry (n = 133), were included in the full analysis. In comparison to compensation reported in AACC SYCL salary surveys conducted in 2010 and 2013, early career median salaries are trending upwards after correction for inflation. SUMMARY: This survey is the first to collect the gender of respondents, and identify a pay gap for some geographic groups. However, this gap could be due in part to a difference in the years of experience, since males were highly represented in the group with >20 years of experience (25 out of 35, 71%). Future studies on compensation trends within clinical chemistry that do not rely on self-report are needed to ensure accuracy and completeness of the dataset.

Tryptophan Metabolism and Its Relationship with Depression and Cognitive Impairment Among HIV-infected Individuals.

OBJECTIVE: Cognitive impairment (CI) and major depressive disorder (MDD) remain prevalent in treated HIV-1 disease; however, the pathogenesis remains elusive. A possible contributing mechanism is immune-mediated degradation of tryptophan (TRP) via the kynurenine (KYN) pathway, resulting in decreased production of serotonin and accumulation of TRP degradation products. We explored the association of these biochemical pathways and their relationship with CI and MDD in HIV-positive (HIV+) individuals. METHODS: In a cross-sectional analysis, concentrations of neopterin (NEO), tumor necrosis factor-alpha, TRP, KYN, KYN/TRP ratio, phenylalanine (PHE), tyrosine (TYR), PHE/TYR ratio, and nitrite were assessed in the cerebrospinal fluid (CSF) and plasma of HIV+ (n = 91) and HIV-negative (HIV-) individuals (n = 66). CI and MDD were assessed via a comprehensive neuropsychological test battery. A Global Deficit Score ≥0.5 was defined as CI. Nonparametric statistical analyses included Kruskal-Wallis and Mann-Whitney U tests, and multivariate logistic regression. RESULTS: Following Bonferroni correction, NEO concentrations were found to be greater in CSF and TRP concentration was found to be lower in the plasma of HIV+ versus HIV- individuals, including a subgroup of aviremic (defined as HIV-1 RNA <50 cps/mL) HIV+ participants receiving antiretroviral therapy (n = 44). There was a nonsignificant trend toward higher KYN/TRP ratios in plasma in the HIV+ group (P = 0.027; Bonferroni corrected α = 0.0027). In a logistic regression model, lower KYN/TRP ratios in plasma were associated with CI and MDD in the overall HIV+ group (P = 0.038 and P = 0.063, respectively) and the aviremic subgroup (P = 0.066 and P = 0.027, respectively), though this observation was not statistically significant following Bonferroni correction (Bonferroni corrected α = 0.0031). CONCLUSIONS: We observed a trend toward lower KYN/TRP ratios in aviremic HIV+ patients with CI and MDD.

Marker expression, behaviors, and responses vary in different lines of conditionally immortalized cultured podocytes.

The state-of-the-art cultured podocyte is conditionally immortalized by expression of a temperature-sensitive mutant of the SV40 large-T antigen. These cultures proliferate at 33°C and differentiate at 37°C into arborized cells that more closely resemble in vivo podocytes. However, the degree of resemblance remains controversial. In this study, several parameters were measured in podocyte cell lines derived from mouse (JR, KE), human (MS), and rat (HK). In all lines, the quantities of NEPH1 and podocin proteins and NEPH1 and SYNPO mRNAs were comparable to glomeruli, while synaptopodin and nephrin proteins and NPHS1 and NPHS2 mRNAs were <5% of glomerular levels. Expression of Wilms' tumor-1 (WT1) mRNA in mouse lines was comparable to glomeruli, but rat and human lines expressed little WT1. Undifferentiated human and mouse lines had similar proliferation rates that decreased after differentiation, while the rate in rat cells remained constant. The motility of different lines varied as measured by both general motility and wound-healing assays. The toxicity of puromycin aminonucleoside was MS ∼ JR >> KE, and of doxorubicin was JR ∼ KE > MS, while HK cells were almost unaffected. Process formation was largely a result of contractile action after formation of lamellipodia. These findings demonstrate dramatic differences in marker expression, response to toxins, and motility between lines of podocytes from different species and even between similarly-derived mouse lines.

A longitudinal study on the impact of antipsychotic treatment on serum leptin in schizophrenia.

OBJECTIVE: The study objective was to explore the biological basis for link between antipsychotic-induced weight gain and therapeutic response in schizophrenia by examining longitudinal changes in serum leptin level after antipsychotic treatment. METHODS: We examined serum leptin in schizophrenia patients at antipsychotic-naive baseline status as well as after 3 months of antipsychotic treatment. For baseline analyses, the patients were compared with healthy controls matched for anthropometric measures and physical activity. RESULTS: At baseline, schizophrenia patients had significantly lower levels of leptin in comparison with controls. After treatment, body mass index and levels of leptin increased significantly in patients. The magnitude of increase in leptin had a significant positive correlation with magnitude of increase in body mass index; the magnitude of reduction in SANS total score showed significant positive correlation with the magnitude of increase in leptin level. CONCLUSION: The study findings suggest a potential role for leptin to mediate the link between antipsychotic-induced weight gain and beneficial therapeutic response in schizophrenia.

Effect of antipsychotic treatment on Insulin-like Growth Factor-1 and cortisol in schizophrenia: a longitudinal study.

Neurodevelopmental pathogenesis of schizophrenia might be mediated by abnormalities in Insulin-like Growth Factor-1 (IGF-1). Developmental disturbances like obstetric complications, by themselves, as well as through the resultant hypercortisolemia due to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, can lead to deficient IGF-1 level. The relevance of IGF-1-Cortisol interactions in schizophrenia, especially in the context of antipsychotic treatment, is yet to be explored. In this study, thirty-three antipsychotic-naïve schizophrenia patients (13-men) were examined for serum IGF-1 and cortisol levels at baseline and after 3months of antipsychotic treatment. For baseline analyses, the patients were compared with 33 healthy controls matched for age, sex, socio-economic status, and physical activity. Symptoms were assessed using Scale for Assessment of Positive Symptoms (SAPS) and Scale for Assessment of Negative Symptoms (SANS). At baseline, schizophrenia patients had significantly lower levels of IGF-1 [t=4.6; p<0.0001] and higher levels of cortisol [t=3.9; p=0.0002] in comparison with healthy controls. Following treatment, IGF-1 level increased significantly [t=4.5; p<0.0001] whereas cortisol decreased significantly [t=2.5; p=0.02] in patients. There was a significant positive correlation between magnitude of increase in IGF-1 level and the magnitude of reduction in cortisol level [r=0.52; p=0.002]. Also, the greater the increase in IGF-1 the greater was the reduction in SAPS score [r=0.39; p=0.02]. Our study findings demonstrate that antipsychotic treatment can result in significant elevation of serum IGF-1 possibly mediated by reduction in cortisol levels. These observations suggest a possible link between HPA axis abnormalities and IGF-1 deficits in the neurodevelopmental pathogenesis of schizophrenia.

Oxidative stress and neopterin abnormalities in schizophrenia: a longitudinal study.

Oxidative stress abnormalities have been proposed to explain the pathogenesis of schizophrenia. The present study examined neopterin and oxidative stress abnormalities in schizophrenia patients before and after treatment. Serum neopterin, total anti-oxidants, nitrites and thiols in antipsychotic-naïve schizophrenia patients (n=45) were assessed at baseline before treatment in comparison with healthy controls (n=43). The schizophrenia patients on treatment were followed up for 3months and these parameters were reassessed (n=32). In comparison to healthy controls, schizophrenia patients had significantly higher levels of neopterin and nitrites and significantly lower levels of anti-oxidants before treatment. During follow-up assessments in schizophrenia patients after treatment with antipsychotics, there was a significant decrease in the neopterin levels and significant increase in anti-oxidant levels. Our study observations support increased oxidative stress in schizophrenia that improves with antipsychotic treatment.

Longitudinal study of beta2-microglobulin abnormalities in schizophrenia.

In an earlier cross-sectional study, we reported antipsychotic-naive schizophrenia patients to have significantly elevated beta2-microglobulin (beta2M) level suggestive of its potential association with the pathogenesis of schizophrenia. In this study, we present the follow-up analyses of beta2M in 31 patients from the previous study who were re-assessed after 92.1+/-7.2 days of antipsychotic treatment. Compared to baseline, there was a further significant elevation of beta2M in schizophrenia patients following treatment, especially in those who were treated with risperidone. Also, there was a significant negative correlation between beta2M level and total psychopathology score during follow-up in risperidone group. The study findings extend further support the role for beta2M in the pathogenesis of schizophrenia strengthening the case for immune dysregulation. Moreover, the observations suggest the possibility that the mechanism of action of antipsychotics might involve alteration of immune parameters.

HIV-1 clade C infection and progressive disruption in the relationship between cortisol, DHEAS and CD4 cell numbers: a two-year follow-up study.

BACKGROUND: It is well established that there is mutual interaction between the neuroendocrines and immune systems and that the disturbance in any one system could affect the function of the other. While there is a large body of evidence suggesting negative impact of human immunodeficiency virus type 1B (HIV-1B) infection on both immune and neuroendocrine systems, the consequence of HIV-1 clade C infection (with structural differences from HIV-1B virus) on these systems is not clearly understood. METHODS: We carried out a 2-year longitudinal study on plasma profile of adrenocorticosteroids, including cortisol and DHEAS and their relationship with declining CD4+ cell counts in neurologically asymptomatic HIV-C infected individuals (N=84) in order to understand the impact of HIV-1 clade C infection on adrenocortical dysfunction and its relationship with the progressive decline in the cell mediated immunity. RESULTS: We found that while plasma cortisol levels increased significantly at baseline in HIV-1C infected individuals compared to those in HIV-negative controls (HIV-1C+, 9.83+/-0.39 vs controls, 8.04+/-0.45; p<0.01), there was a significant decrease in DHEAS in HIV-1C+ individuals, compared to that in HIV-negative controls (81.02+/-4.9 vs 185.1+/-12.03, p<0.001), and consequently a significant increase in cortisol:DHEAS ratio in HIV-1 clade C infected persons (0.19+/-0.002 vs control 0.058+/-0.006; p<0.001). Moreover, in HIV-1C infected individuals, there was a strong positive correlation between DHEAS and CD4 cells (r=0.2; p<0.05), and a strong negative correlation between cortisol, as well as cortisol:DHEAS ratio and CD4 cells (r=-0.25; p<0.01; and r=-0.31; p<0.001, respectively). CONCLUSIONS: These findings suggest the persistent and progressive adrenocortical dysfunction during the asymptomatic phase of HIV infection, and that the evaluation of increase in plasma cortisol, a decrease in DHEAS, and an increase in cortisol:DHEAS ratio may serve as important biomarkers preceding the impending down regulation of CD4 cell counts and progressive decline in the immune system function in HIV-1C infection. Furthermore, these findings may indicate the dysregulation of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity, the enzyme involved in the biosynthesis of cortisol and DHEA through the pregnenolone-progesterone pathway, and that it may offer an opportunity for drug discovery targeting re-regulation of 3beta-HSD activity for potential therapeutic application in HIV-1C infection.

Beta2-microglobulin abnormalities in antipsychotic-naïve schizophrenia: evidence for immune pathogenesis.

Studies examining immune dysfunction in schizophrenia have reported decreased type-1 T-helper cell specific immunity (Th1) and increased type-2 T-helper cell specific immunity (Th2) and related abnormalities in inflammatory system. Beta2-Microglobulin (beta2M) influences the development of dendritic cells, which play a significant role in regulating the differentiation of naive CD4+ T cells into Th1 or Th2 lineages. The present study examined serum beta2M in antipsychotic-naïve schizophrenia patients (n=43) in comparison with age, sex, handedness and socioeconomic status matched healthy controls (n=43). Serum beta2M was significantly higher in schizophrenia patients (1692.6+/-354.4 ng/mL) than healthy controls (1409.6+/-246.9 ng/mL) (t=4.3; p<0.0001). There was a significant positive correlation between beta2M level and total psychopathology score (r=0.32; p=0.035). These novel observations suggest that beta2M abnormalities might have a potential association with the pathogenesis of schizophrenia.

Progressive dysregulation of autonomic and HPA axis functions in HIV-1 clade C infection in South India.

Human immunodeficiency virus type 1 (HIV-1) infection causes a wide spectrum of abnormalities in neurological, neuropsychological, and neuroendocrinological functions. Several studies report disturbance in autonomic nervous system (ANS) and hypothalamic pituitary-adrenal (HPA) axis function in HIV-1B infected individuals. However, no such investigations on the effect of HIV-1 clade C infection, particularly during the initial phase of the disease progression, have been reported. The present investigations were carried out longitudinally over a 2-year period at 12 monthly intervals in clinically asymptomatic HIV-1 clade C seropositive patients (n=120) and seronegative control subjects (n=29). We determined both the basal levels and the dynamic changes in plasma levels of norepinephrine (NE), epinephrine (E), adrenocorticotrophic hormone (ACTH) and cortisol (CORT). Studies were also extended longitudinally (at three separate yearly visits of each participant), to evaluate the response of autonomic and HPA axis to mirror star tracing challenge test (MSTCT) and the values were determined as area under the curve (AUC, corrected for baseline levels of NE, E, ACTH, and CORT). The findings show that the values of basal plasma NE levels, as well as NE response to MSTCT (AUC) at the first visit of HIV-1 seropositive individuals did not differ from those found in the control subjects (NE, pg/ml, HIV-1C=313.5+/-12.7 vs. controls=353.0+/-21.3; p=NS; AUC, HIV-1C=225+/-14.75 vs. controls=232.7+/-19.34; p=NS, respectively). At the subsequent two visits of HIV-1 positive patients however, NE response to MSTCT challenge was progressively attenuated (AUC=235+/-19.5 and 162.7+/-13.6; p<0.01 and 0.05, respectively) compared to that found at the first visit. On the other hand, plasma levels of E as well as E response to MSTCT at the first visit were significantly lower in HIV-1C seropositive individuals compared to those in the control subjects (pg/ml, HIV-1C=77.30+/-5.7 vs. controls=119.1+10.5; p<0.05; AUC, HIV-1C =83.29+/-7.5 vs. controls=172.3+/-18.9; p<0.001), but no further change was observed in AUC of E in response to MSTCT at the two subsequent yearly visits. The basal plasma levels of ACTH in HIV-1C seropositives were not different than in the control subjects (pg/ml: HIV-1C=20.0+/-0.9 vs. controls=23.1+/-1.6; p=NS), but ACTH response to MSTCT in HIV-1C seropositive patients at the first visit was lower than in the controls (AUC, HIV-1C=23.57+/-1.5 vs. controls=30.94+/-3.5; p<0.05), and fluctuated between high and low at the second and third visits (AUC, 28.89+/-2.3 and 21.69+/-2.36, respectively). However, the baseline plasma levels of cortisol as well as the response of cortisol to MSTCT (AUC) in HIV-1C seropositive individuals were higher than in the control subjects at the first visit (mug/dl, HIV-1C=9.83+/-0.39 vs. controls=6.3+/-0.56; p<0.05; AUC, HIV-1C=12.31+/-0.7 vs. control=9.18+/-0.9; p<0.05), and remained high at the two subsequent yearly follow up visits of HIV-1C (AUC, 11.8+/-0.86 and 11.98+/-0.77, respectively). These findings demonstrate attenuated autonomic functions, a disconnection between response of ACTH and cortisol to the MSTCT challenge, and an inverse relationship between plasma levels of catecholamine(s) and cortisol. Since plasma catecholamines and cortisol are the peripheral mediators of the autonomic and HPA axis function, the findings of this study reflect the overall adverse effect of HIV-1C infection on autonomic as well as HPA axis functions. The findings, apart from being the first to demonstrate the progressive dysregulation of autonomic nervous system and HPA axis function among HIV-1C infected seropositive individuals much ahead of the onset of acquired immunodeficiency syndrome (AIDS), also suggest that MSTCT, involving visuoconstructive cognitive abilities, is an effective stressor for unraveling the underlying dysfunctions in the neuroendocrine functions in health and disease.

Insulin and insulin-like growth factor-1 abnormalities in antipsychotic-naive schizophrenia.

OBJECTIVE: The purpose of this study was to examine the evidence for the insulin-like growth factor-1 (IGF-1) deficiency hypothesis in the pathogenesis of schizophrenia. METHOD: The authors examined the fasting plasma levels of glucose, insulin, IGF-1, and cortisol in antipsychotic-naive schizophrenia patients (N=44) relative to age- and sex-matched healthy comparison subjects (N=44). Patients and comparison subjects were also matched for anthropometric measures and physical activity. RESULTS: Schizophrenia patients had a significantly higher mean plasma insulin level as well as a significantly higher mean insulin resistance score relative to healthy comparison subjects. The mean plasma IGF-1 level was significantly lower in patients. IGF-1 levels had a significant negative correlation with plasma insulin levels. The total positive symptoms score as well as the hallucinations subscore had a significant inverse relationship with IGF-1 levels. CONCLUSIONS: Deficient IGF-1 might underlie insulin resistance in schizophrenia. The IGF-1 deficit in antipsychotic-naive schizophrenia patients and its significant correlation with psychopathology scores suggest that IGF-1 might be potentially involved in the pathogenesis of schizophrenia.

Plasma adenosine deaminase activity among HIV1 Clade C seropositives: relation to CD4 T cell population and antiretroviral therapy.

BACKGROUND: Plasma adenosine deaminase and its isoenzymes(s) activities have been used as diagnostic marker for intracellular parasitism, including HIV infection, and malignancy of immune cells. HIV infection being primarily targeted against CD4 cells, it would be of interest to relate the activity of total plasma ADA and isoenzymes fractions to immune status and antiretroviral therapy. METHODS: In the present study, plasma total ADA activity (ADAT) including ADA1 and ADA2 isoenzyme(s) were assayed among HIV seropositive Clade C (n=90) comprising both asymptomatic (n=71) and symptomatic (n=19) and compared with that of HIV seronegatives (n=35). RESULTS: A significant increase in the activity of ADAT (16.30+/-0.80 v/s 6.18+/-0.30) as well as ADA1 (6.50+/-0.42 v/s 2.34+/-0.16) and ADA2 (9.79+/-0.53 v/s 3.85+/-0.23) isoenzyme(s) among the asymptomatic as well as the symptomatic subjects as compared to respective controls was noted. Increase in plasma ADAT activity, including ADA1 and ADA2 isoenzyme(s), were found to have negative correlation with CD4 counts (r, -0.273; p<0.05). The increased plasma ADAT activity among the asymptomatic HIV seropositive with CD4 counts>500 (13.2+/-1.65; p<0.01) as well as those who were on antiretroviral therapy (19.31+/-1.36; p<0.001) was evident. CONCLUSIONS: These findings suggest that plasma ADA can be a sensitive marker of an ongoing biological insult to host tissues either because of infection and/or side effects of medication. Measurement of plasma ADA activity, along with serological evidence for HIV infection may provide an alternate laboratory tool to monitor intracellular parasitism including secondary infection vis a vis the after effects of therapeutic outcome.

HPA axis activity and neuropathogenesis in HIV-1 clade C infection.

A disturbance in the activity of the hypothalamic-pituitary-adrenal (HPA) axis has been reported among individuals with HIV-1 infection. However, these studies have been carried out in the West where the infecting clade is clade B. HIV-1 infection is rapidly spreading in various parts of South East Asia, including India, where the HIV-1 infecting clade is largely clade C. An investigation of HPA axis activity in this type of infection is warranted since there are many structural differences between clades B and C. This study was carried out to investigate whether HIV-1 infection clade C interferes with the functions of the hippocampus and thereby affects the HPA axis. We tested the hypothesis that when hippocampus activity is disturbed, it leads to the development of neuropathogenesis in HIV-1 C-clade infected individuals. This study included asymptomatic HIV-1 seropositive individuals (n=117) and, age-matched, HIV-1 seronegative controls (n=29). Neuroendocrine function of the HPA axis was evaluated using plasma levels of cortisol, ACTH, and DHEA-S, both in the morning (0800-1000 hr) and evening (2000-2200 hr). A significant elevation of cortisol levels during A.M. and P.M. hours was observed in HIV-1 infected individuals when compared to the controls. Interestingly, no significant change in ACTH level was observed in HIV-1 seropositive subjects, either during A.M or P.M. Elevated levels of cortisol in HIV-1 seropositive subjects appear to be independent of ACTH and may be the result of a defective negative feedback mechanism. On the other hand, a significant decrease in the plasma levels of DHEA-S was observed during A.M. and P.M. hours in HIV-1 infected individuals, leading to an increased cortisol to DHEA-S ratio. Since increased levels of cortisol and decreased levels of DHEA-S are related to the development of neuropathogenesis, it is hypothesized that a study of the development of neurocognitive deficits among HIV-1 seropositive individuals in India is warranted.