The Impact of Kidney/Pancreas Transplantation on Peripheral Arterial Disease.

INTRODUCTION: It is unclear whether kidney/pancreas (KP) transplantation will prevent the progression of peripheral arterial disease (PAD) in patients with insulin dependent diabetes (IDDM) and end-stage renal disease. We sought to determine the pre- and posttransplant prevalence of symptomatic PAD and changes in carotid artery intima-media thickness (IMT) in KP recipients. METHODS: In this single center study, outcomes were compared between KP recipients with and without a history of PAD. A subset of recipients underwent pre- and posttransplant IMT measurements. RESULTS: Among the study group (N = 107), 18 (17%) recipients admitted to a pretransplant history of symptomatic PAD, comprised 11 foot infections and 7 amputations (5 minor and 2 major). Baseline characteristics of age, gender, race, years of diabetes, dialysis history, smoking history, years of hypertension, and history of coronary artery disease (CAD) were equivalent between PAD and non-PAD cohorts. At a median follow-up of 60 months (IQR: 28, 110), 16 (15%) KP recipients had suffered a PAD event. In multivariate analysis, a pretransplant history of PAD (hazard ratio [HR] 9.66, p < 0.001) and CAD (HR 3.33, p = 0.04) were independent predictors of posttransplant PAD events. Among a subset of 20 recipients (3 with PAD), mean IMT measurements pretransplant and at a median of 24 (range 18-24) months posttransplant, showed no evidence of disease progression. CONCLUSION: Based on IMT measurements and clinical results, KP transplantation stabilized PAD in most patients, but did not alter outcomes of symptomatic PAD recipients. A pretransplant history of PAD and CAD was an independent predictor of posttransplant PAD events.

Acute Q fever in individuals with acute febrile illness & exposure to farm animals: Clinical manifestations & diagnostic approaches.

Background & objectives Q fever is an important zoonotic disease affecting humans as well as animals. The objective of this study was to assess the burden of Q fever in individuals with acute febrile illness, particularly those in close contact with animals. Various diagnostic methods were also evaluated in addition to clinical examination analysis and associated risk factors. Methods Individuals presenting with acute febrile illness who had animal exposure were enrolled (n=92) in this study. Serum samples were tested using IgG and IgM phase 2 enzyme linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA). The PCR targeting the com1 and IS1111 genes was performed on blood samples. PCR amplicons were sequenced and phylogenetically analysed. Demographic data, symptoms, and risk factors were collected through a structured questionnaire. Results Among individuals with acute febrile illness, 34.7 per cent (32 out of 92) were found to be infected with Coxiella burnetii. PCR exhibited the highest sensitivity among the diagnostic methods employed. The most common clinical manifestations included headache, chills, arthralgia, and fatigue. Individuals engaged in daily livestock-rearing activities were found to be at an increased risk of infection. Interpretation & conclusions Q fever is underdiagnosed due to its varied clinical presentations, diagnostic complexities, and lack of awareness. This study underscores the importance of regular screening for Q fever in individuals with acute febrile illness, particularly those with animal exposure. Early diagnosis and increased awareness among healthcare professionals are essential for the timely management and prevention of chronic complications associated with Q fever.

The Evolution of Diabetes Technology - Options Toward Personalized Care.

OBJECTIVE: Advances in diabetes technology, especially in the last few decades, have transformed our ability to deliver care to persons with diabetes (PWDs). Developments in glucose monitoring, especially continuous glucose monitoring (CGM) systems, have revolutionized diabetes care and empowered our patients to manage their disease. CGM has also played an integral role in advancing automated insulin delivery systems. OBSERVATIONS: Currently available and upcoming advanced hybrid closed-loop systems aim to decrease patient involvement and are approaching the functionality of a fully automated artificial pancreas. Other advances, such as smart insulin pens and daily patch pumps, offer more options for patients and require less complicated and costly technology. Evidence to support the role of diabetes technology is growing, and PWD and clinicians must choose the right type of technology with a personalized strategy to manage diabetes effectively. CONCLUSION AND RELEVANCE: Here, we review currently available diabetes technologies, summarize their individual features, and highlight key patient factors to consider when creating a personalized treatment plan. We also address current challenges and barriers to the adoption of diabetes technologies.

Digital Health and Shared Decision-Making in Diabetes Care - A Survey Initiative in Patients and Clinicians.

OBJECTIVE: To assess the landscape of digital health resources in the United States, better understand the impact of the digital health on shared decision-making, and identify potential barriers and opportunities for progress in the care of persons with diabetes. METHODS: The study consisted of two phases: A qualitative phase in which one-on-one interviews were conducted virtually with 34 physicians (endocrinologists {Endos}: n = 15; primary care physicians {PCPs}: n = 19) between February 11, 2021 and February 18, 2021, and a quantitative phase in which two online, email-based surveys in the English language were conducted between April 16, 2021 and May 17, 2021: one with healthcare professionals (HCP) (n = 403: n = 200 Endos and n = 203 PCPs), and one with persons with diabetes (n = 517: patients with type 1 diabetes, n = 257; patients with type 2 diabetes, n = 260). RESULTS: Diabetes digital health tools were found to be helpful in shared decision-making, but leading barriers include cost, coverage, and lack of time by healthcare professionals. Among diabetes digital health tools, continuous glucose monitoring (CGM) systems were used most commonly and viewed as most effective in improving quality of life and facilitating shared decision-making. Strategies for increasing use of diabetes digital health resources included lower cost, integration into electronic health records, and increased simplicity of tools. CONCLUSION: This study revealed that both Endos and PCPs feel that diabetes digital health tools have an overall positive impact. Integration with telemedicine and simpler, lower cost tools with increased patient access can further facilitate shared decision-making and improved diabetes care and quality of life.

Study of synthesis and characterization of raw bagasse, its char and activated carbon prepared using chemical additive.

This paper reports the use of naturally available raw material as sugarcane bagasse (SB) to prepare cost-effective activated carbon. Activated carbon preparation from SB by using ZnCl2 was carried out by chemical activation method. The raw bagasse, its char and activated carbon were characterized on the basis of iodine number, carbon, hydrogen, nitrogen analysis, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and Brunauer-Emmett-Teller (BET) surface area to check their effectiveness. During activated carbon synthesis, the impregnation ratio of SB and ZnCl2 was maintained at 1:1-1:3 and activation temperature was in the range of 600-900 °C for 1 h. From the characterization study, the highest iodine adsorption of activated carbon was found to be 1140.69 mg/g with a 1:2 ratio at 900 °C whereas char gives an iodine number of 529.63 mg/g at the same temperature. The BET surface area of raw bagasse, its char and activated carbon (SB-Zn2-900) obtained was 4.30, 514.27 and 1386.58 m2/g, respectively, which shows charrification and chemical activation improves surface area. The optimum ratio of impregnation and activation temperature was found to be 1:2 at 900 °C. In this work, activated carbon was successfully prepared and obtained product has better characteristics than previously reported studies.

Elevated hemoglobin A1c level and bariatric surgery complications.

INTRODUCTION: In cardiac and orthopedic surgery, elevated glycosylated hemoglobin (HbA1c) is a modifiable risk factor for postoperative complications. However, in bariatric surgery, there is insufficient evidence to assess the effectiveness of preoperative HbA1c assessment and its association with postoperative complications. The objective of this study was to assess the impact of HbA1c on early postoperative outcomes in bariatric surgery patients. METHODS: Patients who underwent laparoscopic sleeve gastrectomy and laparoscopic Roux-En-Y Gastric Bypass between 2017 and 2018 were selected for a retrospective review from the metabolic and bariatric surgery accreditation and quality improvement program (MBSAQIP) database. The study population of 118,742 patients was analyzed for our primary outcome which was defined as a composite of any postoperative complications occurring within 30 days. Two groups were defined by HbA1c cutoff: comparison point A (≤ 8% vs > 8%) and comparison point B (≤ 10% vs > 10%). Procedure-related complications were also examined on subgroup analysis. Propensity score matching (PSM) was used with one-to-one matching. The complication rates before and after PSM were calculated and assessed by Fisher's exact test and conditional logistic regression, respectively. RESULTS: After PSM, demographic and clinical characteristics were all balanced and elevated HbA1C was not associated with worse outcomes. After adjusting for underlying comorbidities, there was no statistically significant difference seen in the composite outcome for comparison point A HbA1C ≤ 8 and HbA1C > 8 (p = 0.22). For comparison point B, patients with HbA1C ≤ 10 had more composite complications compared to patients with HbA1C > 10 (p < 0.001). Also, on subgroup analysis after PSM for procedure-specific complications, patients above the cutoff threshold of 8 did not have worsened composite outcomes (p = 0.58 and 0.89 for sleeve and bypass, respectively). Again, at cutoff threshold of 10, patients in HbA1C ≤ 10 had more composite complications (p = 0.001 and 0.007 for sleeve and bypass, respectively). CONCLUSION: In this study of bariatric patients, elevated HbA1c > 8% or 10% was not associated with increased postoperative complications. HbA1c lower than 10% was associated with some types of adverse outcomes in this bariatric dataset. More studies are needed to investigate these findings further. A high HbA1c alone may not disqualify a patient from proceeding with bariatric surgery.

American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.

OBJECTIVE: The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers. METHODS: The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RESULTS: This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: (1) screening, diagnosis, glycemic targets, and glycemic monitoring; (2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; (3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; (4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes. CONCLUSIONS: This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.

Management of Hyperglycemia in the Noncritical Care Setting: A Real-World Case-Based Approach With Alternative Insulin- and Noninsulin-Based Strategies.

Insulin remains the mainstay of treatment for inpatient hyperglycemia in the United States and Canada. However, some other countries commonly use noninsulin agents such as metformin and sulfonylureas, and several trials have demonstrated the efficacy and safety of incretin-based agents in patients with type 2 diabetes who are admitted to noncritical care medicine and surgery services. There is a high degree of interest in alternative glucose-lowering strategies to achieve favorable glycemic outcomes with lower risks of hypoglycemia. In this case series, we highlight the challenges of inpatient glycemic management and the need for alternatives to the traditional basal-bolus insulin regimen. Additional investigation will be imperative to validate the safety and efficacy of appropriate insulin and noninsulin treatments and to further develop guidelines that are applicable in real-world hospital settings.

TRANSCULTURAL DIABETES CARE IN THE UNITED STATES - A POSITION STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS.

The American Association of Clinical Endocrinologists (AACE) has created a transculturalized diabetes chronic disease care model that is adapted for patients across a spectrum of ethnicities and cultures. AACE has conducted several transcultural activities on global issues in clinical endocrinology and completed a 3-city series of conferences in December 2017 that focused on diabetes care for ethnic minorities in the U.S. Proceedings from the "Diabetes Care Across America" series of transcultural summits are presented here. Information from community leaders, practicing health care professionals, and other stakeholders in diabetes care is analyzed according to biological and environmental factors. Four specific U.S. ethnicities are detailed: African Americans, Latino/Hispanics, Asian Americans, and Native Americans. A core set of recommendations to culturally adapt diabetes care is presented that emphasizes culturally appropriate terminology, transculturalization of white papers, culturally adapting clinic infrastructure, flexible office hours, behavioral medicine-especially motivational interviewing and building trust-culturally competent nutritional messaging and health literacy, community partnerships for care delivery, technology innovation, clinical trial recruitment and retention of ethnic minorities, and more funding for scientific studies on epigenetic mechanisms of cultural impact on disease expression. It is hoped that through education, research, and clinical practice enhancements, diabetes care can be optimized in terms of precision and clinical outcomes for the individual and U.S. population as a whole.

Imperatorin ameliorates lipopolysaccharide induced memory deficit by mitigating proinflammatory cytokines, oxidative stress and modulating brain-derived neurotropic factor.

BACKGROUND: Lipopolysaccharide (LPS), an endotoxin from the outer membrane of Gram negative bacteria has been reported to cause neuroinflammation and learning and memory deficits. There are reports describing the beneficial effects of Imperatorin (IMP), a naturally occurring furanocoumarin in central nervous system (CNS) disorders such as anxiety and epilepsy. OBJECTIVE: In the current study, we investigated whether IMP protects against LPS mediated memory deficits and neuroinflammation. METHODS: Mice pretreated with IMP (5, 10 mg/kg po) were administered LPS (250 µg/kg ip) for 7 days. Memory was evaluated in the Morris water maze (MWM) and Y maze. The mice were euthanised and different biochemical assessments were carried out to measure oxidative stress and acetyl choline esterase (AChE). Further, evaluation of proinflammatory cytokines such as tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) levels and brain derived neurotrophic factor (BDNF) in hippocampus and cortex of brain were performed. RESULTS: LPS administration caused poor memory retention in both, MWM and Y maze, and caused distinct oxidative stress since decrease in superoxide dismutase (SOD), reduced glutathione (GSH) levels and increased lipid peroxidation were observed. Also, a significant rise was observed in the levels of AChE. Moreover, a rise in TNF-α and IL-6 levels and depleted levels of BDNF were noted. IMP pretreatment reversed LPS induced behavioral and memory disturbances and significantly decreased the oxidative stress and AChE levels. It also reduced TNF-α and IL-6 levels and caused a significant upregulation of BDNF levels. CONCLUSION: Present study highlights the potential neuroprotective role of IMP against LPS mediated cognitive impairment and neuroinflammation.

Innovations in Professional Inpatient Diabetes Education.

PURPOSE OF REVIEW: In the rapidly evolving and complex field of inpatient diabetes, complex care teams of physicians, nurse practitioners, physician assistants, nurses, and pharmacists are challenged to remain well informed of the latest clinical treatments and health care trends. Traditional continuing medical education (CME) and continuing education unit (CEU) strategies that require travel and/or time away from work pose a major barrier. With advancements in technology, there are media and other electronic strategies for delivering CME/ CEU that may overcome these current challenges. RECENT FINDINGS: Electronic and internet-based formats are growing due to their convenience, ease of use, lower cost, and ready access to large audiences. Some formats are already being used such as computer-based programs, simulations, and mobile CMEs and CEUs. Other strategies could be further explored including hospital credentialing, stewardship programs, and interdisciplinary health care professional education. However, there is little data on the utilization and efficacy of these newer formats. While traditional CME/CEU meetings prevail, there is a need and an emerging trend using electronic and internet based strategies that are particularly suited for inpatient diabetes education. These methods show great potential and deserve further exploration and development.

Trigonelline insulates against oxidative stress, proinflammatory cytokines and restores BDNF levels in lipopolysaccharide induced cognitive impairment in adult mice.

Neuroinflammation is said to play a pivotal role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Trigonelline (TRG) is a naturally occurring alkaloid, commonly isolated from fenugreek and coffee beans. In the present study, we investigated whether TRG exerts neuroprotective action against LPS mediated cognitive impairment. Mice pretreated with TRG (50 and 100 mg/kg po) were administered with LPS (250 µg/kg ip) for 7 days. Memory was assessed in the Morris water maze (MWM) and Y maze. LPS administration caused poor memory retention in MWM and Y maze paradigms, and resulted in marked oxidative stress as evidenced by decrease in superoxide dismutase (SOD), reduced glutathione (GSH) levels and increased lipid peroxidation in the hippocampus and cortex. Cholinergic involvement during neuroinflammation was evaluated by measuring levels of acetylcholinesterase (AChE) enzyme. TRG treatment at both the doses reversed LPS induced behavioral and memory disturbances, significantly decreased the oxidative stress and AChE levels in both the hippocampus and cortex. LPS administration also elevated the tumour necrosis factor (TNF-α) and interleukin -6 (IL-6) levels, whereas brain derived neurotrophic factor (BDNF) levels were significantly depleted. TRG pretreatment led to decreased TNF-α and IL-6 levels and caused a significant upregulation of BDNF levels. In conclusion, present study highlights the promising neuroprotective role of TRG against LPS mediated cognitive impairment which could be attributed to reduced oxidative stress, inhibition of proinflammatory cytokines and restoration of BDNF levels.

Graphene-Based "Hot Plate" for the Capture and Destruction of the Herpes Simplex Virus Type 1.

The study of graphene-based antivirals is still at a nascent stage and the photothermal antiviral properties of graphene have yet to be studied. Here, we design and synthesize sulfonated magnetic nanoparticles functionalized with reduced graphene oxide (SMRGO) to capture and photothermally destroy herpes simplex virus type 1 (HSV-1). Graphene sheets were uniformly anchored with spherical magnetic nanoparticles (MNPs) of varying size between ∼5 and 25 nm. Fourier-transform infrared spectroscopy (FT-IR) confirmed the sulfonation and anchoring of MNPs on the graphene sheets. Upon irradiation of the composite with near-infrared light (NIR, 808 nm, 7 min), SMRGO (100 ppm) demonstrated superior (∼99.99%) photothermal antiviral activity. This was probably due to the capture efficiency, unique sheet-like structure, high surface area, and excellent photothermal properties of graphene. In addition, electrostatic interactions of MNPs with viral particles appear to play a vital role in the inhibition of viral infection. These results suggest that graphene composites may help to combat viral infections including, but not only, HSV-1.

The Time Is Now: Diabetes Fellowships in the United States.

PURPOSE OF REVIEW: Diabetes is a complex and costly chronic disease that is growing at an alarming rate. In the USA, we have a shortage of physicians who are experts in the care of patients with diabetes, traditionally endocrinologists. Therefore, the majority of patients with diabetes are managed by primary care physicians. With the rapid evolution in new diabetes medications and technologies, primary care physicians would benefit from additional focused and intensive training to manage the many aspects of this disease. Diabetes fellowships designed specifically for primary care physicians is one solution to rapidly expand a well-trained workforce in the management of patients with diabetes. RECENT FINDINGS: There are currently two successful diabetes fellowship programs that meet this need for creating more expert diabetes clinicians and researchers outside of traditional endocrinology fellowships. We review the structure of these programs including funding and curriculum as well as the outcomes of the graduates. The growth of the diabetes epidemic has outpaced current resources for readily accessible expert diabetes clinical care. Diabetes fellowships aimed for primary care physicians are a successful strategy to train diabetes-focused physicians. Expansion of these programs should be encouraged and support to grow the cadre of clinicians with expertise in diabetes care and improve patient access and outcomes.

Is rule of halves still an occurrence in South India: Findings from community-based survey in a selected urban area of Puducherry.

BACKGROUND: The objective of the present study was to assess the applicability of the rule of halves in an urban population of Puducherry, South India. We also aimed to find the correlates associated with undiagnosed hypertension to facilitate targeted screening. METHODOLOGY: We derive our observation from a community-based cross-sectional study conducted using the World Health Organization STEPwise approach to surveillance in urban slum of Puducherry during 2014-15. Blood pressure (BP) was measured for all the study subjects (n = 2399), and the subjects were classified as hypertensive using Joint National Committee 8 criteria, systolic BP (SBP) ≥140 mm Hg and/or diastolic BP (DBP) ≥90 mmHg and/or known hypertensives and/or treatment with antihypertensive drugs. Controlled hypertension was defined as SBP <140 mmHg and DBP <90 mmHg. RESULTS: Of 2399, 799 (33.3%; 95% confidence interval [CI]: 31.4%-35.2%) adults were found to have raised BP by any means (known and unknown hypertensives). Of the 799, 367 (15.3%; 95%CI: 13.9%-16.8%) of study participants were known hypertensives. Of the known hypertensives, 74.7% (274/367) were put on treatment (drugs and or lifestyle modification), and 80% (218/274) were on regular treatment. Higher proportions of men were found to have undiagnosed hypertension compared to women (26.1 vs. 19.8%, P < 0.001). Similarly, adult from below poverty line (23.8 vs. 20%, P < 0.001), unskilled laborer (26.6 vs. 20%, P < 0.001), and literacy less than middle school (12.3 vs. 23%, P < 0.001) had more undiagnosed hypertension. CONCLUSION: In the selected urban area of Puducherry around one-third of the adult populations are having hypertension, including the 54% of undiagnosed hypertension. Adults from the vulnerable subgroups such as lower level of literacy, below poverty line, and unskilled work are found to have higher proportions of undiagnosed hypertension.

Effect of vestibular stimulation on spatial and verbal memory in college students.

BACKGROUND.: Excessive stress may have an adverse effect on learning and memory of students. It was reported that stimulation of the vestibular system enhances memory through its connections with the hippocampus, limbic system and neo cortex. This study aims to assess the effectiveness of vestibular stimulation in the modulation of memory in healthy human subjects. METHODS.: For this longitudinal follow-up study, we assessed spatial and verbal memory of participants followed by vestibular stimulation. A total of 240 healthy college students of 18-24 years, of either sex were selected after obtaining written consent from them. Participants were randomly assigned into four groups-control male and female group and vestibular male and female groups. Vestibular stimulation was administered by making the participants swing on a swing, according to their comfort (back to front direction) as standardized by previous methods. Spatial and verbal memory tests were used to assess memory. Data were analysed using two-way ANOVA followed by the Bonferroni post-hoc tests to compare differences between groups. RESULTS.: Baseline values of spatial and verbal memory scores were not significantly different between the control and intervention groups. Significant enhancement was observed in spatial memory following vestibular stimulation in males but not female subjects. Contrary to this, significant decrease in spatial memory was observed in both males and females due to pre-examination stress who did not receive any vestibular stimulation. Significant enhancement was observed in verbal memory scores in both males and females who received vestibular stimulation, whereas verbal memory was significantly decreased in males and females in the control groups during the pre-examination period. CONCLUSION.: Our study provides evidence to support vestibular stimulation as an efficient method to enhance memory and to prevent pre-examination associated stress-induced changes on memory. We recommend vestibular stimulation as a simple approach to improve verbal memory among students to cope with their pre-examination stress.

2,3-Di-O-picolinyl building blocks as glycosyl donors with switchable stereoselectivity.

2-O-Picolinyl protected glycosyl donors lead to the formation of 1,2-trans glycosides with complete stereoselectivity. This is due to the participatory effect of the picolinyl nitrogen that is able to block the bottom face of the ring via a six-membered cyclic intermediate. Herein we demonstrate that if the nitrogen atom of the O-picolinyl moiety is temporarily blocked by coordination to the metal center (Pd), it becomes unavailable to participate in glycosylation and hence the stereoselectivity of 2-O-picolinyl-assisted glycosylations can be "switched".

Validation of a Biomarker Panel and Longitudinal Biomarker Performance for Early Detection of Ovarian Cancer.

OBJECTIVES: Longitudinal multimarker combinations have the potential to improve sensitivity while maintaining the high specificity required for the early detection of ovarian cancer. The use of multiple markers to improve sensitivity over cancer antigen 125 (CA125) in longitudinal algorithms for early ovarian cancer detection requires the selection of markers with optimal discriminatory power and low longitudinal variance relative to disease-initiated changes. Our objective was to identify a multimarker panel suitable for ovarian cancer, where each individual marker has its own baseline, permitting longitudinal algorithm development. MATERIALS AND METHODS: In this retrospective study, we measured CA125, human epididymis protein 4 (HE4), matrix metalloproteinase-7 (MMP-7), CA72-4, CA19-9, CA15-3, carcinoembryonic antigen, and soluble vascular cell adhesion molecule (sVCAM) concentrations using immunoassays in pretreatment sera from 142 stage I ovarian cancer cases and 5 annual samples each from 217 healthy controls. After random division into training and validation sets, all possible biomarker combinations were explored exhaustively using linear classifiers to identify the panel with the greatest sensitivity for stage I disease at a high specificity of 98%. To evaluate longitudinal performance of the individual markers, the within-person over time and the between-person coefficient of variation (CV) were estimated. Hierarchical modeling across women of log-concentrations enabled the borrowing of information across subjects to moderate variance estimates given the small number of observations per subject. RESULTS: The 4-marker panel comprising CA125, HE4, MMP-7, and CA72-4 performed with the highest sensitivity (83.2%) at 98% specificity. The within-person CVs were lower for CA125, HE4, MMP-7, and CA72-4 (15%, 25%, 25%, and 21%, respectively) compared with their corresponding between-person CV (49%, 20%, 35%, and 84%, respectively) indicating baselines in healthy volunteers. After simple log-transformations, the within-volunteer variation across volunteers was modeled with a normal distribution permitting parsimonious hierarchical modeling. CONCLUSIONS: The multiplex panel chosen is suitable for the early detection of ovarian cancer and the individual markers have their own baseline permitting longitudinal algorithm development.

2-Acylamido analogues of N-acetylglucosamine prime formation of chitin oligosaccharides by yeast chitin synthase 2.

Chitin, a homopolymer of ß1,4-linked N-acetylglucosamine (GlcNAc) residues, is a key component of the cell walls of fungi and the exoskeletons of arthropods. Chitin synthases transfer GlcNAc from UDP-GlcNAc to preexisting chitin chains in reactions that are typically stimulated by free GlcNAc. The effect of GlcNAc was probed by using a yeast strain expressing a single chitin synthase, Chs2, by examining formation of chitin oligosaccharides (COs) and insoluble chitin, and by replacing GlcNAc with 2-acylamido analogues of GlcNAc. Synthesis of COs was strongly dependent on inclusion of GlcNAc in chitin synthase incubations, and N,N'-diacetylchitobiose (GlcNAc2) was the major reaction product. Formation of both COs and insoluble chitin was also stimulated by GlcNAc2 and by N-propanoyl-, N-butanoyl-, and N-glycolylglucosamine. MALDI analyses of the COs made in the presence of 2-acylamido analogues of GlcNAc showed they that contained a single GlcNAc analogue and one or more additional GlcNAc residues. These results indicate that Chs2 can use certain 2-acylamido analogues of GlcNAc, and likely free GlcNAc and GlcNAc2 as well, as GlcNAc acceptors in a UDP-GlcNAc-dependent glycosyltransfer reaction. Further, formation of modified disaccharides indicates that CSs can transfer single GlcNAc residues.

THE RATIONALE FOR USE OF INCRETINS IN THE MANAGEMENT OF NEW ONSET DIABETES AFTER TRANSPLANTATION (NODAT).

OBJECTIVE: Owing to advances in transplant science, increasing numbers of patients are receiving solid organ transplantation. New onset diabetes after transplantation (NODAT) frequently develops in transplant patients and requires acute and often ongoing management of hyperglycemia. The metabolic derangements of NODAT are similar to those of classic type 2 diabetes, and treatment has typically followed diabetes standards of care. Best practices for NODAT management remain to be developed. METHODS: The mechanistic suitability of incretins to treat NODAT pathogenesis has been hitherto underappreciated. This review details the specific mechanistic value of incretins in patients with immunosuppression-associated hyperglycemia. RESULTS: Corticosteroids have long been known to exert their effects on glucose metabolism by decreasing glucose utilization and enhancing hepatic gluconeogenesis. Corticosteroids also significantly and directly reduce insulin secretion, as do calcineurin inhibitors (CNIs), another commonly used group of immunosuppressive drugs that cause hyperglycemia and NODAT. The ability of incretins to counteract immunosuppressant-induced disruptions in insulin secretion suggest that the insulinotropic, glucagonostatic, and glucose-lowering actions of incretins are well suited to treat immunosuppressant-induced hyperglycemia in NODAT. Additional benefits of incretins include decreased glucagon levels and improved insulin resistance. In the case of glucagon-like peptide-1 (GLP-1) receptor agonists, weight loss is another benefit, countering the weight gain that is a common consequence of both hyperglycemia and transplantation. These benefits make incretins very attractive and deserving of more investigation. CONCLUSION: Among diabetes treatment options, incretin therapies uniquely counteract immunosuppressant drugs' interference with insulin secretion. We propose an incretin-based treatment paradigm for NODAT management.