Predicting methotrexate resistance in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is an incurable, systemic autoimmune disease that decreases quality of life and can lead to severe disability. While there are many medications available to treat RA, the first-line of therapy is low-dose methotrexate (MTX), a small molecule disease-modifying anti-rheumatic drug (DMARD). MTX is the recommended therapy due to its affordability and efficacy in reducing symptoms in most RA patients. Unfortunately, there is great person-to-person variability in the physiological response to MTX, with up to 50% of patients showing little response to the medication. Thus, many RA patients initially placed on MTX do not experience an adequate reduction of symptoms, and could have benefited more in both the short and long terms if initially prescribed a different drug that was more effective for them. To combat this problem and better guide treatment decisions, many research groups have attempted to develop predictive tools for MTX response. Currently, there is no reliable, clinical-grade method to predict an individual's response to MTX treatment. In this review, we describe progress made in the area of MTX non-response/resistance in RA patients. We specifically focus on application of the following elements as predictive markers: proteins related to MTX transport and function, intracellular MTX concentration, immune cell frequencies, cytokines, and clinical factors.

Identification of Anti-Long Chain Saturated Fatty Acid IgG Antibodies in Serum of Patients with Type 2 Diabetes.

High levels of serum long chain saturated fatty acids (LCSFAs) have been associated with inflammation in type 2 diabetes. Dietary SFAs can promote inflammation, the secretion of IgG antibodies, and secretion of the proinflammatory cytokine IL-1ß. This study characterizes anti-LCSFA IgG antibodies from patients with type 2 diabetes. Serum samples from several cohorts with type 2 diabetes were analyzed for the presence of anti-LCSFA IgG, the cytokine IL-1ß, and nonesterified fatty acids. Anti-LCSFA IgG was isolated from patient samples and used for in vitro characterization of avidity and specificity. A cohort participating in En Balance, a diabetes health education program that improved diabetes management, tested positive for anti-LCSFA IgG. Following the 3-month program, the cohort showed a significant reduction in anti-LCSFA IgG levels. Anti-LCSFA antibodies isolated from these patients demonstrated high avidity, were specific for long chain SFAs, and correlated with serum fatty acids in patients with managed type 2 diabetes. Interestingly, anti-LCSFA IgG neutralized PA-induced IL-1ß secretion by dendritic cells. Our data shows that nonesterified SFAs are recognized by IgG antibodies present in human blood. The identification of anti-LCSFA IgG antibodies in human sera establishes a basis for further exploration of lipid induced immune responses in diabetic patients.

Effect of Group Medical Appointments on Glycemic Control of Patients With Type 2 Diabetes.

Rationale. To evaluate the effectiveness of group medical appointments (GMAs) for patients with type 2 diabetes. Objective. To compare A1C levels of patients participating in GMAs to those of patients who received usual primary care. Design and methods. This study was a retrospective electronic chart review comparing GMA care for 52 male patients to usual primary care for 52 male patients. Demographic (age, marital status, and ethnicity/race) and health-related (height, weight, BMI, duration of diabetes, use of alcohol and tobacco, and A1C) variables were analyzed. Results. A greater proportion of GMA patients (50%) versus usual primary care patients (19.2%) reached target A1C goals (P = 0.001). GMA participants also had a significantly faster rate of decline in A1C over time compared to usual primary care patients (P < 0.001). Conclusion. This study demonstrated that the concept of medical management delivered in a group approach had a positive effect on glycemic control in patients with type 2 diabetes. GMAs were found to be an effective approach to achieving patient-centered goals for improving the glycemic control of patients with type 2 diabetes.

Active Medical Learner Engagement Results in the Discovery That One Size Does Not Fit All in Overcoming COVID-19 Vaccine Hesitancy.

Vaccine hesitancy is an ongoing public health concern defined as the refusal of a vaccine that is readily available. Therefore, we developed a project to explore why patients in a safety net medical center were hesitant or refused the COVID-19 vaccine. The project was conducted by healthcare learners to promote "learning by doing". Responses were collected through a previously developed and ongoing survey among both hospitalized and ambulatory patients that had no previous history of COVID-19 infection, were currently infected, or had recovered from COVID-19. Results were analyzed using a priori power analysis and Chi-squared test. We discovered that different self-reported ethnic groups had different reasons for vaccine hesitancy; specifically, 69% of Black/African American respondents stated that their main reason for hesitancy was vaccine safety compared to 13.9% of non-Hispanic Whites (p = 0.005). Furthermore, our cohort was significantly more likely to disagree rather than agree with the statement: "getting vaccinated is important for the health of others in my community"(p = 0.016). The learners discovered that a more specific approach to vaccine education would be required to understand and overcome vaccine hesitancy in our cohort of socioeconomic and ethnically diverse groups.

A CTB-SARS-CoV-2-ACE-2 RBD Mucosal Vaccine Protects Against Coronavirus Infection.

Mucosal vaccines protect against respiratory virus infection by stimulating the production of IgA antibodies that protect against virus invasion of the mucosal epithelium. In this study, a novel protein subunit mucosal vaccine was constructed for protection against infection by the beta coronavirus SARS-CoV-2. The vaccine was assembled by linking a gene encoding the SARS-CoV-2 virus S1 angiotensin converting enzyme receptor binding domain (ACE-2-RBD) downstream from a DNA fragment encoding the cholera toxin B subunit (CTB), a mucosal adjuvant known to stimulate vaccine immunogenicity. A 42 kDa vaccine fusion protein was identified in homogenates of transformed E. coli BL-21 cells by acrylamide gel electrophoresis and by immunoblotting against anti-CTB and anti-ACE-2-RBD primary antibodies. The chimeric CTB-SARS-CoV-2-ACE-2-RBD vaccine fusion protein was partially purified from clarified bacterial homogenates by nickel affinity column chromatography. Further vaccine purification was accomplished by polyacrylamide gel electrophoresis and electro-elution of the 42 kDa chimeric vaccine protein. Vaccine protection against SARS-CoV-2 infection was assessed by oral, nasal, and parenteral immunization of BALB/c mice with the CTB-SARS-CoV-2-ACE-2-RBD protein. Vaccine-induced SARS-CoV-2 specific antibodies were quantified in immunized mouse serum by ELISA analysis. Serum from immunized mice contained IgG and IgA antibodies that neutralized SARS-CoV-2 infection in Vero E6 cell cultures. In contrast to unimmunized mice, cytological examination of cell necrosis in lung tissues excised from immunized mice revealed no detectable cellular abnormalities. Mouse behavior following vaccine immunization remained normal throughout the duration of the experiments. Together, our data show that a CTB-adjuvant-stimulated CTB-SARS-CoV-2-ACE-2-RBD chimeric mucosal vaccine protein synthesized in bacteria can produce durable and persistent IgA antibodies in mice that neutralize the SARS-CoV-2 subvariant Omicron BA.1.1.

Regulatory and Interacting Partners of PDLIM7 in Thyroid Cancer.

Enigma protein, encoded by the PDLIM7 gene, is overexpressed in thyroid cancer in a stage-dependent manner, suggesting a potential involvement in the initiation and progression of thyroid cancer. The Enigma interacts with several cellular pathways, including PI3K/AKT, MDM2, and BMP-1. The Enigma is regulated by microRNAs. Specifically, we showed that the Enigma protein upregulation corresponds to the downregulation of Let-7 family genes. There is limited research on the interactions and regulation of the Enigma with other proteins/genes in thyroid cancer tissues, indicating a gap in current knowledge. Our aim is to establish the Enigma as a biomarker. We also aim to study the interacting partners of the Enigma signaling pathways and their probable miRNA regulation in thyroid cancer progression. Using Western blotting, densitometric analysis, immunoprecipitation (IP), and reverse IP, we detected the protein expression and protein-protein interactions in the corresponding papillary thyroid carcinomas (PTCs). Utilizing real-time qPCR assay and Pearson's correlation test, we highlighted the correlation between PDLIM7 and Let-7g gene expression in the same tissues. The results showed the differential upregulations of the Enigma protein in different stages of PTCs compared to benign tissues along with AKT, VDR, BMP-1, and MDM2 proteins. Loss of DBP was observed in a subset of PTCs. Strong interactions of the Enigma with PI3K/AKT and MDM2 were noted, along with a weaker BMP-1 interaction. Pearson's correlation coefficient analysis between PDLIM7 and let-7g gene expression was significant (p < 0.05); however, there was a weak inverse correlation (r = -0.27). The study suggests the potential utility of the PDLIM7-qPCR assay as a biomarker for thyroid cancer. The Enigma's interactions with key signaling pathways may provide valuable insights into the development of thyroid cancer. The study contributes to understanding the molecular mechanisms involving the Enigma protein in thyroid cancer and highlights its potential as a biomarker.

The En Balance Spanish diabetes education program improves apolipoproteins, serum glucose and body composition in Hispanic diabetics.

OBJECTIVE: We evaluated the changes in apolipoproteins, glycemic status, and body composition after 3 months using a culturally sensitive diabetes education program, En Balance, in diabetic Hispanics. METHODS: Thirty-four (9 males, 25 females) Hispanic diabetics participated in the En Balance program over three months. Body composition was determined by dual energy X-ray absorptiometry (DXA), fasting plasma glucose (FPG), A1c, and apolipoproteins (Apo) measured after 3 months participation. Differences were analyzed using paired t testing and relationships between changes in Apo, A1c, total cholesterol, body mass index and body composition by Spearman correlations. RESULTS: Completion of En Balance resulted in a significant reduction in weight (80.31 +/- 1.97 kg vs 81.25 +/- 17.97 kg, P = .015), FPG (143.21 +/- 57.8 mg/dL vs 166.41 +/- 65.9 mg/dL P = .003), and A1c (7.08 +/- 1.6% vs 7.87 +/- 2.0%, P = < .001). DXA demonstrated reduction in total fat (29.54 +/- 10.0 kg vs 30.24 +/- 11.80 kg, P = < .001) and trunk fat (15.09 +/- 5.6 kg vs 16.87 +/- 5.4 kg, P = .001). High density lipoprotein significantly increased (48.85 +/- 11.4 vs 44.65 +/- 8.8, P = .002) and total serum cholesterol/high density lipoprotein ratio decreased (3.87 +/- .98 vs 4.35 +/- 1.0, P = .001). There were significant correlations at three months between changes in Apo A1 and A2 (r = .559, P < .001), Apo E and total cholesterol (r = .746, P < .001), between A1c and FPG (r = .563, P = .001) and BMI and body weight (r = .732, P < .001). CONCLUSIONS: The En Balance program improved body composition, A1c, FPG, total cholesterol/HDL ratio and HDL. If these trends can be sustained, En Balance may serve as a unique educational paradigm for improving type 2 diabetes in Hispanics.

Dietary Omega-3 Polyunsaturated Fatty-Acid Supplementation Upregulates Protective Cellular Pathways in Patients with Type 2 Diabetes Exhibiting Improvement in Painful Diabetic Neuropathy.

BACKGROUND: Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed to improve chronic neuroinflammatory diseases in peripheral and central nervous systems. For instance, docosahexaenoic acid (DHA) protects nerve cells from noxious stimuli in vitro and in vivo. Recent reports link PUFA supplementation to improving painful diabetic neuropathy (pDN) symptoms, but cellular mechanisms responsible for this therapeutic effect are not well understood. The objective of this study is to identify distinct cellular pathways elicited by dietary omega-3 PUFA supplementation in patients with type 2 diabetes mellitus (T2DM) affected by pDN. METHODS: Forty volunteers diagnosed with type 2 diabetes were enrolled in the "En Balance-PLUS" diabetes education study. The volunteers participated in weekly lifestyle/nutrition education and daily supplementation with 1000 mg DHA and 200 mg eicosapentaenoic acid. The Short-Form McGill Pain Questionnaire validated clinical determination of baseline and post-intervention pain complaints. Laboratory and untargeted metabolomics analyses were conducted using blood plasma collected at baseline and after three months of participation in the dietary regimen. The metabolomics data were analyzed using random forest, hierarchical clustering, ingenuity pathway analysis, and metabolic pathway mapping. RESULTS: The data show that metabolites involved in oxidative stress and glutathione production shifted significantly to a more anti-inflammatory state post supplementation. Example of these metabolites include cystathionine (+90%), S-methylmethionine (+9%), glycine cysteine-glutathione disulfide (+157%) cysteinylglycine (+19%), glutamate (-11%), glycine (+11%), and arginine (+13.4%). In addition, the levels of phospholipids associated with improved membrane fluidity such as linoleoyl-docosahexaenoyl-glycerol (18:2/22:6) (+253%) were significantly increased. Ingenuity pathway analysis suggested several key bio functions associated with omega-3 PUFA supplementation such as formation of reactive oxygen species (p = 4.38 × 10-4, z-score = -1.96), peroxidation of lipids (p = 2.24 × 10-5, z-score = -1.944), Ca2+ transport (p = 1.55 × 10-4, z-score = -1.969), excitation of neurons (p = 1.07 ×10-4, z-score = -1.091), and concentration of glutathione (p = 3.06 × 10-4, z-score = 1.974). CONCLUSION: The reduction of pro-inflammatory and oxidative stress pathways following dietary omega-3 PUFA supplementation is consistent with the promising role of these fatty acids in reducing adverse symptoms associated with neuroinflammatory diseases and painful neuropathy.

Decisions to Choose COVID-19 Vaccination by Health Care Workers in a Southern California Safety Net Medical Center Vary by Sociodemographic Factors.

BACKGROUND: Limited information exists regarding COVID-19 vaccine hesitancy among healthcare workers (HCWs). Our previous survey analyzed the reasons for HCWs' decisions to accept vaccination, suggesting that a "one-size fits all" approach may not suffice to increase vaccine uptake. METHODS: Based on the vaccination acceptance group (acceptor, hesitant, refuser), we examined differences by sociodemographic factors (race/ethnicity, household income, education) from Likert Scale responses to fourteen influences affecting a decision to be vaccinated using the Kruskal-Wallis test and multinomial logistic regression with mutual adjustment for these sociodemographic factors, age, and sex. RESULTS: Non-Hispanic White vaccine acceptors ranked lower confidence in preventing, withstanding, or treating COVID-19, while Non-Hispanic Blacks more highly regarded the motivation of a religious leader, colleague, or family member. Social media was ranked more influential among Non-Hispanic Asians. Acceptors with lower incomes ranked a job requirement influential; conversely, higher income vaccine hesitant HCWs highly rated this reason. More highly educated acceptors ranked being motivated by colleagues, family, and other HCWs higher. Adjustment weakened some but not all the differences between groups. CONCLUSIONS: Sociodemographic factors affect HCWs' decisions to be vaccinated against COVID-19. Our findings may help develop more focused and tailored strategies to improve vaccination acceptance.

Long-term, progressive, aerobic training increases adiponectin in middle-aged, overweight, untrained males and females.

Adipose tissue secretes the adipokine, adiponectin (ADPN), which increases insulin sensitivity. Because some of the metabolic effects of exercise and ADPN are similar, exercise has been proposed to increase ADPN. However, most short-term (≤3 mos) and constant-effort exercise protocols have not produced increases in ADPN. Furthermore, no direct comparisons of male and female subjects on the effect of exercise on ADPN levels have been reported. We hypothesized that long-term (6 mos), progressive training would increase ADPN levels in both males and females. We recruited middle-aged, untrained males and females to participate in an interventional study employing a marathon training regimen progressing from 9.7 to 88.5 km (6 to 55 miles) per week over 6 mos. At baseline, we matched the mean ages of the male and female groups. We collected and stored fasting plasma samples and recorded body measurements at 0 (baseline) and 6 mos. Stored samples were analysed for insulin, glucose, and ADPN. ADPN increased significantly among both males (from 5.89 ± 2.46 (mean ± SD) to 7.65 ± 3.18 µg/ml; p < 0.05) and females (from 8.48 ± 3.22 to 10.56 ± 4.05 µg/ml; p < 0.05). The extent of the increase in ADPN was similar in the male (40.7 ± 50%; median, 12.1%) and female (27.0 ± 31.1%; median, 22.3%) groups. However, there was no significant reduction in insulin resistance as measured by the HOMA-IR scores in either group. We conclude that long-term, progressive aerobic training increases circulating ADPN levels in middle-aged, untrained males and females.

Correlates of COVID-19 Vaccine Acceptance, Hesitancy and Refusal among Employees of a Safety Net California County Health System with an Early and Aggressive Vaccination Program: Results from a Cross-Sectional Survey.

Since health professionals provide frontline care to COVID-19 patients, information on vaccine acceptance among healthcare workers is needed. We developed and implemented an anonymous internet-based cross-sectional survey with direct solicitation among employees of a safety net health system. Items queried demographic and health-related characteristics, experience with and knowledge of COVID-19, and determinants of decisions to vaccinate. COVID-19 vaccine acceptance groups (acceptors, hesitant, refusers) were defined; an adapted version of the WHO vaccine hesitancy scale was included. The survey demonstrated good reliability (Cronbach's alpha = 0.92 for vaccine hesitancy scale; 0.93 for determinants). General linear and logistic regression methods examined factors which were univariately associated with vaccine hesitancy and vaccine acceptance, respectively. Multivariable models were constructed with stepwise model-building procedures. Race/ethnicity, marital status, job classification, immunocompromised status, flu vaccination and childhood vaccination opinions independently predicted hesitancy scale scores. Gender, education, job classification and BMI independently predicted acceptance, hesitancy, and refusal groups. Among hesitant employees, uncertainty was reflected in reports of motivating factors influencing their indecision. Despite a strong employee-support environment and job protection, respondents reported physical and mental health effects. The appreciation of varied reasons for refusing vaccination should lead to culturally sensitive interventions to increase vaccination rates amongst healthcare workers.

Does teaching Optimism lower Burnout in residency training- a pilot study.

Background: Residents frequently experience burnout. Multiple interventions to decrease the risk of burnout have had inconsistent results. In non-medical settings, improving optimism promotes a positive outlook and enhances well-being. Thus, psychological interventions that improve optimism could have potential to decrease the risk for burnout. Objective: Using Lazarus' Ways of Coping as an organizational framework, this intervention sought to evaluate the impact of an optimism curriculum on residents' burnout. Methods: Thirty-six Internal Medicine residents participated in an optimism improvement program from November 2019 to April 2020. We determined pre- and post-curriculum measures of optimism, happiness, and burnout with validated surveys. The Optimism Curriculum was comprised of three one-hour long sessions, which included lectures, group and self-reflective exercises. A post - curriculum evaluation rating the effectiveness of the program was administered separately. Results: Thirty-four out of thirty-six residents completed the post curricular surveys. Individuals with low optimism scores had a higher score for burnout compared to those with higher optimism scores. The post-intervention survey showed numerical improvement in optimism, happiness and burnout, although these changes were not statistically significant. The post-intervention survey showed a decrease in the measure of burnout; however, this was not significant (p = 0.24) with an effect size of 0.34 (Cohen's d). Conclusions: Teaching optimism to residents with the objective of decreasing the risk of burnout is feasible and easily integrated into residency education sessions. The encouraging results of this pilot study lay the foundation for additional studies and suggest a practical role for implementing optimism curricula in residency training programs.

En Balance: The Contribution of Physical Activity to the Efficacy of Spanish Diabetes Education of Hispanic Americans with Type 2 Diabetes.

PURPOSE: En Balance, a culturally sensitive diabetes education program, improves glycemic control in Hispanics with type 2 diabetes. The program emphasized diet, physical activity, and other factors important for glycemic control. However, the individual contributions of these education factors are unclear. The purpose of this study is to assess the contribution of physical activity to the success of En Balance in improving the health of Mexican Americans with type 2 diabetes. METHODS: A retrospective study was conducted with plasma samples collected pre- and post-3-month study. Samples from 58 (18 males and 40 females) Hispanic subjects with type 2 diabetes were analyzed for the concentration of kynurenines, known to decrease in response to exercise. After three months, health outcomes for the active group (decreased kynurenines) and the rest of the cohort were evaluated by paired Wilcoxon signed-rank test. RESULTS: Half of the subjects had increased kynurenine levels at the end of the educational program. We found that the subjects in the active group with decreased kynurenine concentrations displayed statistically greater improvements in fasting blood glucose, A1C, cholesterol, and triglycerides despite weight loss being higher in the group with increased kynurenine concentrations. CONCLUSIONS: En Balance participants with decreased kynurenine levels had significantly improved glycemic control. These data suggest that physical activity significantly contributes to the success of the En Balance education program. This analysis indicates that diabetes public health educators should emphasize the benefit of physical activity on glycemic control even in the absence of major weight loss.

Initial experience with patient-clinician secure messaging at a VA medical center.

The authors implemented what is possibly the first secure messaging system in a VA Medical Center. Since reimbursement for secure messaging is not of great concern and clinical data systems are fully computerized, several evaluation strategies were used to assess clinical adoption. To address known concerns of clinicians, the authors analyzed secure messaging use and performed a content analysis. Message volumes were low and content analysis demonstrated that messages were appropriate. Despite this, a clinician survey showed that clinical adoption was impeded by several factors including the introduction of secure messaging to selected patients, workload concerns, and clinician communication preferences. In addition, the authors believe that clinicians experienced clinical adoption inertia resulting from the overload of information in a highly computerized clinical environment. The authors learned that to promote clinician adoption they must demonstrate workload benefits from secure messaging and more fully analyze the clinical computing workload that clinicians experience.

Effects of omega-3 polyunsaturated fatty-acid supplementation on neuropathic pain symptoms and sphingosine levels in Mexican-Americans with type 2 diabetes.

PURPOSE: To determine whether dietary supplementation with omega-3 polyunsaturated fatty acids (PUFAs) reduces neuropathic pain symptoms in Mexican-Americans with type 2 diabetes. METHODS: Forty volunteers with type 2 diabetes enrolled in the "En Balance-PLUS" program, which provided weekly nutrition-diabetes education and daily supplementation with 1,000 mg docosahexaenoic acid (DHA)-200 mg eicosapentaenoic acid over 3 months. The study assessed self-reported neuropathic pain symptoms pre/postintervention using the short-form McGill Pain Questionnaire (SF-MPQ), monitored clinical laboratory values at baseline and 3 months, and performed baseline and 3-month metabolomic analysis of plasma samples. RESULTS: A total of 26 participants self-reported neuropathic pain symptoms at baseline. After 3 months of omega-3 PUFA supplementation, participants reported significant improvement in SF-MPQ scores (sensory, affective, and visual analogue scale; P<0.001, P=0.012, and P<0.001, respectively). Untargeted metabolomic analysis revealed that participants in the moderate-high SF-MPQ group had the highest relative plasma sphingosine levels at baseline compared to the low SF-MPQ group (P=0.0127) and the nonpain group (P=0.0444). Omega-3 PUFA supplementation increased plasma DHA and reduced plasma sphingosine levels in participants reporting neuropathic pain symptoms (P<0.001 and P<0.001, respectively). Increased plasma DHA levels significantly correlated with improved SF-MPQ sensory scores (r=0.425, P=0.030). Improved SF-MPQ scores, however, did not correlate with clinical/laboratory parameters. CONCLUSION: The data suggest that omega-3 PUFAs dietary supplementation may reduce neuropathic pain symptoms in individuals with type 2 diabetes and correlates with sphingosine levels in the plasma.

Improved clinical outcomes using a culturally sensitive diabetes education program in a Hispanic population.

PURPOSE: The purpose of this study was to evaluate the effects of a culturally sensitive diabetes education program for Hispanics with type 2 diabetes. METHODS: This study is a prospective cohort study to test the impact of a comprehensive diabetes education program on blood glucose control on Hispanics with type 2 diabetes. The educational program focused on maintaining glycemic control and general aspects of managing diabetes and complications. The study participants were recruited by flyers placed in Hispanic markets and in ambulatory care clinics. A total of 34 Hispanic male and female subjects with type 2 diabetes participated in the study. The concentrations of glucose, insulin, hemoglobin A1c (HbA1c), total cholesterol, triglycerides, low-density lipoprotein and high-density lipoprotein (HDL) cholesterol were analyzed at baseline and at 3 months. RESULTS: A significant mean change was observed for HbA1c, fasting plasma glucose, cholesterol/HDL ratio, and HDL after 3 months of education compared with baseline. There were significant reductions in weight, total fat, percent fat, trunk fat, and waist-to-hip ratio compared with baseline. After 3 months, subjects showed a significant positive correlation between changes in body mass index and insulin and weight, total fat, trunk fat, and fat free mass and insulin. CONCLUSIONS: A culturally sensitive program conducted in Spanish had a significant impact on important clinical parameters in Hispanic subjects with diabetes in a relatively short time period. The study demonstrates the importance of designing education intervention studies that are sensitive to cultural diversity, particularly in at-risk diabetic subjects.

Pituitary Apoplexy Presenting as Ophthalmoplegia and Altered Level of Consciousness without Headache.

Background. Pituitary apoplexy (PA) is a clinical syndrome caused by acute ischemic infarction or hemorrhage of the pituitary gland. The typical clinical presentation of PA includes acute onset of severe headache, visual disturbance, cranial nerve palsy, and altered level of consciousness. Case Report. A 78-year-old man presented to the emergency department with one-day history of ptosis and diplopia and an acute-onset episode of altered level of consciousness which was resolving. He denied having headache, nausea, or vomiting. Physical examination revealed third-cranial nerve palsy and fourth-cranial nerve palsy both on the right side. Noncontrast computed tomography (CT) scan of the head was unremarkable. Brain magnetic resonance imaging (MRI) showed a pituitary mass with hemorrhage (apoplexy) and extension to the right cavernous sinus. The patient developed another episode of altered level of consciousness in the hospital. Transsphenoidal resection of the tumor was done which resulted in complete recovery of the ophthalmoplegia and mental status. Conclusion. Pituitary apoplexy can present with ophthalmoplegia and altered level of consciousness without having headache, nausea, or vomiting. A CT scan of the head could be negative for hemorrhage. A high index of suspicion is needed for early diagnosis and timely management of pituitary apoplexy.

Extracellular vimentin modulates human dendritic cell activation.

Vimentin is an intermediate filament protein traditionally considered to be an intracellular protein with a structural role. However, recent evidence suggests that vimentin can also be found outside the cell in disease conditions such as cancer, traumatic tissue injury, and inflammation. Extracellular vimentin was previously found to stimulate innate immunity by increasing monocyte and macrophage ability to kill bacteria. However, vimentin has also been previously found to decrease neutrophil infiltration into inflamed tissue. How extracellular vimentin affects the initiation of adaptive immune responses is unknown. Initiation of adaptive immunity involves priming of naïve T cells by antigen-presenting cells, the most effective of which are dendritic cells (DCs). In this study, we demonstrate how extracellular vimentin modulates lipopolysaccharide (LPS) - induced activation of human DCs. Using cytometric bead arrays, we show that extracellular vimentin decreases LPS-activated DC secretion of pro-inflammatory cytokines IL-6 and IL-12 while increasing secretion of the anti-inflammatory cytokine IL-10. Using flow cytometry, we show that extracellular vimentin does not significantly affect LPS-induced DC surface expression of MHC I (HLA-ABC) or MHC II (HLA-DR) presentation molecules, costimulatory factors (CD80, CD86), or the DC maturation marker (CD83). Further, LPS-stimulated DCs co-cultured with allogeneic naïve CD4 + T cells (Th0) induced less secretion of the pro-inflammatory Th1 effector cytokine IFN-γ in the presence of vimentin than in the presence of LPS alone. This result suggests that vimentin reduces Th1 differentiation. Taken together, our data suggest that extracellular vimentin may inhibit pro-inflammatory adaptive immune responses, by blocking DC secretion of pro-inflammatory cytokines. Thus, extracellular vimentin may play an important role in cancer or trauma-complications by inducing suppression of the adaptive immune response. In a positive sense, the presence of extracellular vimentin may prevent tissue-damage from contributing to the development of autoimmunity. Consequently, extracellular vimentin may become a novel drug target for treatment of a variety of pro- and anti-inflammatory disease conditions.

Approach to the provision of transgender health care in a veteran population.

Transgender patients often experience health disparities, including higher rates of psychiatric comorbidity, tobacco and substance use disorders, higher suicide risk, and reduced access and initiation of medical and mental health services. In 2011, the Department of Veterans Affairs (VA) health care system released a directive outlining the provision of transgender health care services. Since 2011, the number of transgender veterans seeking services has increased. To address these health care disparities and ensure competent comprehensive medical and mental health care for this population, an interprofessional team collaborated to develop the first formalized Transgender Healthcare Clinic at the VA Loma Linda Medical Center. The team consisted of an endocrinologist, primary care provider, clinical pharmacist, psychologist, and social worker. Each member of the team plays a key role in the management of mental and medical health care for transgender veterans. After implementation of the Transgender Healthcare Clinic and its respective model for appointments, access to gender transition-related health care has improved and expanded. Although the role of the clinical pharmacist is well established in this clinic, the addition of a psychiatric pharmacist to the transgender health care team could improve patient care through the integration of an expert understanding of behavioral and pharmacologic aspects facing transgender individuals. The psychiatric pharmacist is trained with the unique skill set required to address these concerns and facilitate the optimal management of co-occurring mental illnesses commonly seen in this patient population. Further research focusing on the integration of psychiatric pharmacists into transgender health care teams is needed.

Pathologic significance of a novel oncoprotein in thyroid cancer progression.

BACKGROUND: The incidence of thyroid cancer is increasing worldwide, and there is an emerging need to develop accurate tools for diagnosis. Fine needle aspiration biopsy has greatly improved evaluation of thyroid nodules, but challenges with indeterminate lesions remain in up to 25% of biopsies. Novel tissue biomarkers may assist in improved nodule characterization. Microcalcifications occurring in thyroid cancers suggest proteins involved in bone formation may play a role in thyroid carcinogenesis. We evaluated the expression of the known osteogenic protein, Enigma, in thyroid cancer as a candidate oncoprotein and role in carcinogenesis based on association with other known oncoproteins such as bone morphogenetic protein-1 (BMP-1). METHODS: The expression of both Enigma and BMP-1 were evaluated by immunohistochemistry (IHC) in an equal number of benign (n = 120) and different histological subtypes of malignant (n = 120) human archival thyroid nodules with and without calcification. The colocalization of Enigma with BMP-1 was evaluated by confocal microscopy using the BZ analyzer. RESULTS: Enigma was strongly expressed in thyroid cancer tissue with a higher immunoreactive score in advanced thyroid cancer compared to less advanced and benign nodules. Enigma was localized either in cytoplasm or nucleus depending on the histological subtypes. Higher expression of Enigma was associated with the tumor size and lymph node involvement. There was clear and strong colocalization signal of Enigma and that of BMP-1. Expression of Enigma occurred without regard to calcification in cancer tissue. CONCLUSION: Enigma may serve as an oncoprotein marker, identifying benign from malignant thyroid tissue on FNA. Enigma may have a role in carcinogenesis of thyroid cancer independent of tissue calcification, possibly in relation to interaction with BMP-1.