Use of therapeutic plasma exchange to remove lipoprotein X in a patient with vanishing bile duct syndrome presenting with cholestasis, pseudohyponatremia, and hypercholesterolemia: A case report and review of literature.

INTRODUCTION: Lipoprotein X (Lp-X) is an abnormal lipoprotein found in multiple disease conditions, including liver dysfunction and cholestasis. High Lp-X concentrations can interfere with some laboratory testing that may result in spurious results. The detection of Lp-X can be challenging, and there is currently a lack of consensus regarding the management of Lp-X other than treating the underlying disease. CASE PRESENTATION: A 42-year-old female with Hodgkin's lymphoma treated with dexamethasone, high dose cytarabine and cisplatin and vanishing bile duct syndrome confirmed by liver biopsy presented with cholestasis, pseudohyponatremia (sodium, 113 mmol/L; reference range 136-146 mmL/L; serum osmolality, 303 mOsm/kg), and hypercholesterolemia (> 2800 mg/dL, reference range < 200 mg/dL). Lp-X was confirmed by lipoprotein electrophoresis (EP). Although she did not manifest any specific signs or symptoms, therapeutic plasma exchange (TPE) was initiated based on laboratory findings of extreme hypercholesterolemia, spuriously abnormal serum sodium, and HDL values, and the potential for short- and long-term sequelae such as hyperviscosity syndrome, xanthoma, and neuropathy. During the hospitalization, she was treated with four 1.0 plasma volume TPE over 6 days using 5% albumin for replacement fluid. After the first TPE, total cholesterol (TC) decreased to 383 mg/dL and sodium was measured at 131 mmol/L. The patient was transitioned into outpatient maintenance TPE to eliminate the potential of Lp-X reappearance while the underlying disease was treated. Serial follow-up laboratory testing with lipoprotein EP showed the disappearance of Lp-X after nine TPEs over a 10-week period. LITERATURE REVIEW: There are seven and four case reports of Lp-X treated with TPE and lipoprotein apheresis (LA), respectively. While all previous case reports showed a reduction in TC levels, none had monitored the disappearance of Lp-X after completing a course of therapeutic apheresis. CONCLUSION: Clinicians should have a heightened suspicion for the presence of abnormal Lp-X in patients with cholestasis, hypercholesterolemia, and pseudohyponatremia. Once Lp-X is confirmed by lipoprotein EP, TPE should be initiated to reduce TC level and remove abnormal Lp-X. Most LA techniques are not expected to be beneficial since Lp-X lacks apolipoprotein B. Therefore, we suggest that inpatient course of TPE be performed every other day until serum sodium, TC and HDL levels become normalized. Outpatient maintenance TPE may also be considered to keep Lp-X levels low while the underlying disease is treated. Serum sodium, TC, and HDL levels should be monitored while on maintenance TPE.

Performance of Anti-Carbamylated Protein Antibody Testing in the Routine Evaluation of Rheumatoid Arthritis from a Single Center.

BACKGROUND: Detection of anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factors (RF) in sera support the diagnosis of rheumatoid arthritis (RA); however, these markers are not detected in about 20% of RA patients. More recently, antibodies against carbamylated proteins (anti-CarP) have emerged with implications for preclinical RA diagnosis. The objective of this study was to assess the clinical performance of anti-CarP and correlate with disease severity in routine clinical practice. METHODS: Retrospective chart review of 331 subjects submitted for RA panel serology: 136 clinically defined RA-positive and 195 RA-negative patients. Fifty additional individuals were recruited for healthy controls. Patients' sera were tested for anti-CCP, anti-CarP, and RF antibodies. Clinical performance characteristics were evaluated for anti-CarP individually and in combination with anti-CCP and RF. Documented erosions and synovitis were correlated with anti-CarP positivity. RESULTS: Anti-CarP had a clinical sensitivity and specificity of 27% and 94%, respectively, for established RA. This sensitivity was lower than anti-CCP (79%) and RF (85%). The specificity of anti-CarP was similar to anti-CCP (93%) and higher than RF (69%). Anti-CarP in combination with anti-CCP and RF increased specificity (100%) but decreased sensitivity (21%). There was no correlation of anti-CarP positivity with presence of bone erosions; however, there was an increase in anti-CarP positivity among patients with synovitis. CONCLUSIONS: Anti-CarP demonstrates high specificity in diagnosis of established RA but lacks clinical sensitivity. In combination, anti-CarP does not improve clinical performance of anti-CCP and RF but may be useful in anti-CCP negative patients and in identifying patients with more active disease.

Human Pseudoislet System for Synchronous Assessment of Fluorescent Biosensor Dynamics and Hormone Secretory Profiles.

The pancreatic islets of Langerhans, which are small 3D collections of specialized endocrine and supporting cells interspersed throughout the pancreas, have a central role in the control of glucose homeostasis through the secretion of insulin by beta cells, which lowers blood glucose, and glucagon by alpha cells, which raises blood glucose. Intracellular signaling pathways, including those mediated by cAMP, are key for regulated alpha and beta cell hormone secretion. The 3D islet structure, while essential for coordinated islet function, presents experimental challenges for mechanistic studies of the intracellular signaling pathways in primary human islet cells. To overcome these challenges and limitations, this protocol describes an integrated live-cell imaging and microfluidic platform using primary human pseudoislets generated from donors without diabetes that resemble native islets in their morphology, composition, and function. These pseudoislets are size-controlled through the dispersion and reaggregation process of primary human islet cells. In the dispersed state, islet cell gene expression can be manipulated; for example, biosensors such as the genetically encoded cAMP biosensor, cADDis, can be introduced. Once formed, pseudoislets expressing a genetically encoded biosensor, in combination with confocal microscopy and a microperifusion platform, allow for the synchronous assessment of fluorescent biosensor dynamics and alpha and beta cell hormone secretory profiles to provide more insight into cellular processes and function.

Gynecological surgery in adulthood imparts cognitive and brain changes in rats: A focus on hysterectomy at short-, moderate-, and long-term intervals after surgery.

Premenopausal hysterectomy is associated with a greater relative risk of dementia. We previously demonstrated cognitive impairments in adult rats six weeks after hysterectomy with ovarian conservation compared with intact sham-controls and other gynecological surgery variations. Here, we investigated whether hysterectomy-induced cognitive impairments are transient or persistent. Adult rats received sham-control, ovariectomy (Ovx), hysterectomy, or Ovx-hysterectomy surgery. Spatial working memory, reference memory, and anxiety-like behavior were tested either six-weeks post-surgery, in adulthood; seven-months post-surgery, in early middle-age; or twelve-months post-surgery, in late middle-age. Hysterectomy in adulthood yielded spatial working memory deficits at short-, moderate-, and long-term post-surgery intervals. Serum hormone levels did not differ between ovary-intact, but differed from Ovx, groups. Hysterectomy had no significant impact on healthy ovarian follicle or corpora lutea counts for any post-surgery timepoint compared with intact sham-controls. Frontal cortex, dorsal hippocampus, and entorhinal cortex were assessed for activity-dependent markers. In entorhinal cortex, there were alterations in FOSB and ΔFOSB expression during the early middle-age timepoint, and phosphorylated ERK1/2 levels at the adult timepoint. Collectively, results suggest a primary role for the uterus in regulating cognition, and that memory-related neural pathways may be modified following gynecological surgery. This is the first preclinical report of long-term effects of hysterectomy with and without ovarian conservation on cognition, endocrine, ovarian, and brain assessments, initiating a comprehensive framework of gynecological surgery effects. Translationally, findings underscore critical needs to decipher how gynecological surgeries, especially those involving the uterus, impact the brain and its functions, the ovaries, and overall aging from a systems perspective.

Evaluations of memory, anxiety, and the growth factor IGF-1R after post-surgical menopause treatment with a highly selective progestin.

Progestogens are a key component of menopausal hormone therapies. While some progestogens can be detrimental to cognition, there is preclinical evidence that progestogens with a strong progesterone-receptor affinity benefit some molecular mechanisms believed to underlie cognitive function. Thus, a progestin that maximizes progesterone-receptor affinity and minimizes affinities to other receptors may be cognitively beneficial. We evaluated segesterone-acetate (SGA), a 19-norprogesterone derivative with a strong progesterone-receptor affinity and no androgenic or estrogenic-receptor activity, hypothesizing that it would enhance cognition. Middle-aged rats underwent Sham or Ovariectomy (Ovx) surgery followed by administration of medroxyprogesterone-acetate (MPA; used as a positive control as we have previously shown MPA-induced cognitive deficits), SGA (low or high dose), or vehicle (one Sham and one Ovx group). Spatial working and reference memory, delayed retention, and anxiety-like behavior were assessed, as were memory- and hormone- related protein assays within the frontal cortex, dorsal hippocampus, and entorhinal cortex. Low-dose SGA impaired spatial working memory, while high-dose SGA had a more extensive detrimental impact, negatively affecting spatial reference memory and delayed retention. Replicating previous findings, MPA impaired spatial reference memory and delayed retention. SGA, but not MPA, alleviated Ovx-induced anxiety-like behaviors. On two working memory measures, IGF-1R expression correlated with better working memory only in rats without hormone manipulation; any hormone manipulation or combination of hormone manipulations used herein altered this relationship. These findings suggest that SGA impairs spatial cognition after surgical menopause, and that surgical menopause with or without progestin administration disrupts relationships between a growth factor critical to neuroplasticity.

Inherited causes of exocrine pancreatic insufficiency in pediatric patients: clinical presentation and laboratory testing.

Pediatric patients with exocrine pancreatic insufficiency (EPI) have symptoms that include abdominal pain, weight loss or poor weight gain, malnutrition, and steatorrhea. This condition can be present at birth or develop during childhood for certain genetic disorders. Cystic fibrosis (CF) is the most prevalent disorder in which patients are screened for EPI; other disorders also are associated with pancreatic dysfunction, such as hereditary pancreatitis, Pearson syndrome, and Shwachman-Diamond syndrome. Understanding the clinical presentation and proposed pathophysiology of the pancreatic dysfunction of these disorders aids in diagnosis and treatment. Testing pancreatic function is challenging. Directly testing aspirates produced from the pancreas after stimulation is considered the gold standard, but the procedures are not standardized or widely available. Instead, indirect tests are often used in diagnosis and monitoring. Although indirect tests are more widely available and easier to perform, they have inherent limitations due to a lack of sensitivity and/or specificity for EPI.

Quantification of 5-Hydroxyindoleacetic Acid in Urine by Ultra-performance Liquid Chromatography Tandem Mass Spectrometry.

Serotonin (5-hydroxytryptamine) is a neurotransmitter produced in excess by carcinoid tumors, which develop from enterochromaffin cells. 5-Hydroxyindoleacetic acid (5-HIAA) is the primary urinary metabolite of serotonin, making measurement of 5-HIAA useful in the diagnosis and management of carcinoid tumors. Here we describe a simple, inexpensive, and fast method for the detection and quantification of 5-HIAA in urine. Samples are prepared by simple 1:1 dilution. The instrumental analysis is performed by chromatographic separation on a reverse-phase analytical column followed by detection using a triple quadrupole mass spectrometer with electrospray ionization in positive ion mode. Data are acquired by multiple reaction monitoring (MRM).

Task-dependent learning and memory deficits in the TgF344-AD rat model of Alzheimer's disease: three key timepoints through middle-age in females.

The TgF344 rat model of Alzheimer's disease (AD) provides a comprehensive neuropathology presentation, with age-dependent development of tau tangles, amyloid-beta (A[Formula: see text]) plaques, neuronal loss, and increased gliosis. The behavioral trajectory of this model, particularly relating to spatial learning and memory, has yet to be fully characterized. The current experiment evaluated spatial working and reference memory performance, as well as several physiological markers of health, at 3 key age points in female TgF344-AD rats: 6-months, 9-months, and 12-months. At 6 months of age, indications of working and reference memory impairments were observed in transgenic (Tg) rats on the water radial-arm maze, a complex task that requires working and reference memory simultaneously; at 12 months old, Tg impairments were observed for two working memory measures on this task. Notably, no impairments were observed at the 9-month timepoint on this maze. For the Morris maze, a measure of spatial reference memory, Tg rats demonstrated significant impairment relative to wildtype (WT) controls at all 3 age-points. Frontal cortex, entorhinal cortex, and dorsal hippocampus were evaluated for A[Formula: see text]1-42 expression via western blot in Tg rats only. Analyses of A[Formula: see text]1-42 expression revealed age-dependent increases in all 3 regions critical to spatial learning and memory. Measures of physiological health, including heart, uterine, and body weights, revealed unique age-specific outcomes for female Tg rats, with the 9-month timepoint identified as critical for further research within the trajectory of AD-like behavior, physiology, and pathology.

Ovarian Hormones Regulate Nicotine Consumption and Accumbens Glutamatergic Plasticity in Female Rats.

Women report greater cigarette cravings during the menstrual cycle phase with higher circulating levels of 17ß-estradiol (E2), which is metabolized to estrone (E1). Both E2 and E1 bind to estrogen receptors (ERs), which have been highly studied in the breast, uterus, and ovary. Recent studies have found that ERs are also located on GABAergic medium spiny neurons (MSNs) within the nucleus accumbens core (NAcore). Glutamatergic plasticity in NAcore MSNs is altered following nicotine use; however, it is unknown whether estrogens impact this neurobiological consequence. To test the effect of estrogen on nicotine use, we ovariectomized (OVX) female rats that then underwent nicotine self-administration acquisition and compared them to ovary-intact (sham) rats. The OVX animals then received either sesame oil (vehicle), E2, or E1+E2 supplementation for 4 or 20 d before nicotine sessions. While both ovary-intact and OVX females readily discriminated levers, OVX females consumed less nicotine than sham females. Further, neither E2 nor E1+E2 increased nicotine consumption back to sham levels following OVX, regardless of the duration of the treatment. OVX also rendered NAcore MSNs in a potentiated state following nicotine self-administration, which was reversed by 4 d of systemic E2 treatment. Finally, we found that E2 and E1+E2 increased ERα mRNA in the NAcore, but nicotine suppressed this regardless of hormone treatment. Together, these results show that estrogens regulate nicotine neurobiology, but additional factors may be required to restore nicotine consumption to ovary-intact levels.

Evaluating the Cognitive Impacts of Drospirenone, a Spironolactone-Derived Progestin, Independently and in Combination With Ethinyl Estradiol in Ovariectomized Adult Rats.

Oral contraceptives and hormone therapies require a progestogen component to prevent ovulation, curtail uterine hyperplasia, and reduce gynecological cancer risk. Diverse classes of synthetic progestogens, called progestins, are used as natural progesterone alternatives due to progesterone's low oral bioavailability. Progesterone and several synthetic analogs can negatively impact cognition and reverse some neuroprotective estrogen effects. Here, we investigate drospirenone, a spironolactone-derived progestin, which has unique pharmacological properties compared to other clinically-available progestins and natural progesterone, for its impact on spatial memory, anxiety-like behavior, and brain regions crucial to these cognitive tasks. Experiment 1 assessed three drospirenone doses in young adult, ovariectomized rats, and found that a moderate drospirenone dose benefited spatial memory. Experiment 2 investigated this moderate drospirenone dose with and without concomitant ethinyl estradiol (EE) treatment, the most common synthetic estrogen in oral contraceptives. Results demonstrate that the addition of EE to drospirenone administration reversed the beneficial working memory effects of drospirenone. The hippocampus, entorhinal cortex, and perirhinal cortex were then probed for proteins known to elicit estrogen- and progestin- mediated effects on learning and memory, including glutamate decarboxylase (GAD)65, GAD67, and insulin-like growth factor receptor protein expression, using western blot. EE increased GAD expression in the perirhinal cortex. Taken together, results underscore the necessity to consider the distinct cognitive and neural impacts of clinically-available synthetic estrogen and progesterone analogs, and why they produce unique cognitive profiles when administered together compared to those observed when each hormone is administered separately.

Clinical and Analytical Characterization of the DiaSorin and ScheBo Fecal Pancreatic Elastase 1 Assays.

OBJECTIVES: Fecal pancreatic elastase (PE) assays are screening tests for exocrine pancreatic insufficiency (EPI). We analytically evaluated a new PE assay and retrospectively analyzed data from an academic hospital and reference laboratory to understand the clinical utility. METHODS: Forty stool samples with different PE concentrations were tested on the ScheBo enzyme-linked immunosorbent assay (ELISA) versus DiaSorin LIAISON immunoassay; a simple-to-use extraction device was assessed. The cross-reactivity of porcine enzymes was investigated in the immunoassay. Charts of 207 patients with PE results less than 250 µg/g at an academic hospital were reviewed, and data were analyzed for 5136 patients with repeat PE results from a reference laboratory. RESULTS: The LIAISON immunoassay gave comparable results to the ScheBo ELISA, with 87.5% agreement of PE results in classifying as sufficient, mild/moderate insufficiency, or severe insufficiency. The extraction device worked well compared with manual weighing, and no cross reactivity with porcine enzymes was observed. In agreement with prior studies, our clinical data suggested that PE assays were most useful in detecting severe EPI. CONCLUSIONS: The new DiaSorin LIAISON immunoassay preforms similarly to the well-known ScheBo ELISA. Pancreatic elastase assays can help identify patients with severe EPI but are not as useful in classifying mild/moderate EPI.

Clinical Utility and Analytical Aspects of Direct Measurements of Free Hormones Using Mass Spectrometry-Based Methods.

BACKGROUND: The free hormone (FH) hypothesis states that hormone action and the corresponding biological effects are mediated by the unbound (free) fraction of hormone in circulation. The in vivo relationship between protein-bound and FH is complex and dynamic. In most individuals, measurement of total hormone (TH) is usually adequate to reflect the hormone status; however, certain physiological conditions and/or medications can affect protein binding and alter FH concentration. In these cases, measurement of FH will provide a better measure of the bioactive hormone status than measurement of the TH. Measurement of FH presents many challenges, as the concentrations are very low and there are number of pitfalls, which may affect the measured concentrations. CONTENT: In this review, we discuss techniques used in the separation and direct quantitation of FH concentrations in biological samples using mass spectrometry for analysis. We also highlight clinical situations in which FH analysis is warranted and when mass spectrometry should be the preferred methodology over immunoassays. SUMMARY: Equilibrium dialysis, ultrafiltration, or size-exclusion separation coupled with liquid chromatography-tandem mass spectrometry provides a sensitive and specific method to measure FH concentrations. These direct methods are useful in iatrogenic or physiological states that alter hormone binding or metabolism.

Mitigation of Biotin Interference in Manual and Automated Immunoassays by Preconjugating Biotinylated Antibodies to the Streptavidin Surface as an Alternative to Biotin Depletion.

BACKGROUND: Streptavidin-to-biotin binding is one of the strongest noncovalent interactions in nature and incorporated into many immunoassays. Biotin-streptavidin coupling assays are susceptible to interference from free biotin in patient specimens, which may falsely decrease or increase results. To prevent biotin interference, we evaluated a method to preconjugate biotinylated antibodies to the assay's streptavidin solid surface before adding patient specimen and compared this technique to a biotin depletion protocol. METHODS: Biotin interference in 3 manual ELISAs and 2 automated immunoassays was established. Mitigation of biotin interference by preincubation was evaluated in each assay by adding biotinylated antibody to the streptavidin-coated surface before adding biotin- or PBS-spiked serum. Lastly, the preincubation method was compared to a biotin-depletion protocol to compare the effectiveness of mitigating biotin interference. RESULTS: In the presence of 400 µg/L biotin, analyte detection was reduced to 10% to 15% of total in the ELISA assays and to 15.2% in the automated sandwich (thyroglobulin) immunoassay. In the automated competitive (free thyroxine) immunoassay, biotin caused an increased detection of 551.6%. Preconjugation of the biotinylated capture antibody to the streptavidin surface in the ELISA assays resulted in 84% to 99% activity recovery, compared to 84% to 97% by a biotin depletion protocol. Similarly, automated sandwich and competitive immunoassays obtained 97.1% and 116.5% recovery by preconjugation, compared to 95.6% and 100.3% by the depletion method, respectively. CONCLUSION: This study demonstrates how assay redesign to include preconjugation of biotinylated capture antibody to streptavidin is an effective alternative to biotin-depletion methods to mitigate biotin interference.

Mistaken Identity: The Role of Autoantibodies in Endocrine Disease.

BACKGROUND: Autoimmune endocrine diseases can be thought of as a case of mistaken identity. The immune system mistakenly attacks one's own cells, as if they were foreign, which typically results in endocrine gland hypofunction and inadequate hormone production. Type 1 diabetes mellitus and autoimmune thyroid disorders (Hashimoto and Graves diseases) are the most common autoimmune endocrine disorders, while conditions such as Addison disease are encountered less frequently. Autoantibody production can precede clinical presentation, and their measurement may aid verification of an autoimmune process and guide appropriate treatment modalities. CONTENT: In this review, we discuss type 1 diabetes mellitus, autoimmune thyroid disorders, and Addison disease, emphasizing their associated autoantibodies and methods for clinical detection. We will also discuss efforts to standardize measurement of autoantibodies. CONCLUSIONS: Autoimmune endocrine disease progression may take months to years and detection of associated autoantibodies may precede clinical onset of disease. Although detection of autoantibodies is not necessary for diagnosis, they may be useful to verify an autoimmune process.

Concordance of Umbilical Cord Drug Screening in Multiple Births: Experience from a Reference Laboratory and Academic Medical Center.

The objective of this study was to review the results of umbilical cord drug screening in twins and triplets (multiples) to compare the detected drug(s) and/or drug metabolite(s). Results that did not agree between multiples were considered mismatched and investigated. A retrospective analysis was conducted using de-identified data from a national reference laboratory, and results were compared with data from an academic medical center, where detailed medical chart review was performed. Umbilical cord was analyzed for stimulants, sedatives, opioids and other drugs and metabolites. For the reference laboratory dataset, 23.3% (n = 844) of 3,616 umbilical cords from twins (n = 3,550) or triplets (n = 66) were positive for one or more drugs and/or metabolites. Of these, mismatched results were identified for 37 sets of twins (2.1%) and no sets of triplets. The most frequent mismatches were found in opioids (n = 24), with morphine (n = 5) being the most mismatched of any single analyte in the panel. Mismatches for the marijuana metabolite 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (9-COOH-THC) in the reference laboratory dataset occurred in 6 of 737 sets of twins (0.8%) and no triplets. For the academic medical center dataset, 21.9% (n = 57) of 260 umbilical cords tested positive for one or more drugs and/or metabolite(s). Of these, four mismatches (3.2%) were identified, including 9-COOH-THC (n = 2), phentermine (n = 1) and oxycodone (n = 1), all involving twins. All involved cases where the discrepant analyte was likely present in the negative twin but either slightly below the reporting cutoff threshold or failed analytical quality criteria. Mismatched results of umbilical cord drug screening occur in less than 4% of twins and most often occur when the analyte is slightly above the reporting cutoff in just one infant.

Surgical Menopause and Estrogen Therapy Modulate the Gut Microbiota, Obesity Markers, and Spatial Memory in Rats.

Menopause in human females and subsequent ovarian hormone deficiency, particularly concerning 17ß-estradiol (E2), increase the risk for metabolic dysfunctions associated with obesity, diabetes type 2, cardiovascular diseases, and dementia. Several studies indicate that these disorders are also strongly associated with compositional changes in the intestinal microbiota; however, how E2 deficiency and hormone therapy affect the gut microbial community is not well understood. Using a rat model, we aimed to evaluate how ovariectomy (OVX) and subsequent E2 administration drive changes in metabolic health and the gut microbial community, as well as potential associations with learning and memory. Findings indicated that OVX-induced ovarian hormone deficiency and E2 treatment had significant impacts on several health-affecting parameters, including (a) the abundance of some intestinal bacterial taxa (e.g., Bifidobacteriaceae and Porphyromonadaceae), (b) the abundance of microbial short-chain fatty acids (SCFAs) (e.g., isobutyrate), (c) weight/BMI, and (d) high-demand spatial working memory following surgical menopause. Furthermore, exploratory correlations among intestinal bacteria abundance, cognition, and BMI underscored the putative influence of surgical menopause and E2 administration on gut-brain interactions. Collectively, this study showed that surgical menopause is associated with physiological and behavioral changes, and that E2-linked compositional changes in the intestinal microbiota might contribute to some of its related negative health consequences. Overall, this study provides novel insights into interactions among endocrine and gastrointestinal systems in the post-menopausal life stage that collectively alter the risk for the development and progression of cardiovascular, metabolic, and dementia-related diseases.

The Rhesus Macaque as a Translational Model for Neurodegeneration and Alzheimer's Disease.

A major obstacle to progress in understanding the etiology of normative and pathological human brain aging is the availability of suitable animal models for experimentation. The present article will highlight our current knowledge regarding human brain aging and neurodegeneration, specifically in the context of Alzheimer's disease (AD). Additionally, it will examine the use of the rhesus macaque monkey as a pragmatic translational animal model in which to study underlying causal mechanisms. Specifically, the discussion will focus on behavioral and protein-level brain changes that occur within the central nervous system (CNS) of aged monkeys, and compare them to the changes observed in humans during clinically normative aging and in AD.

Hereditary pancreatitis in a young adult: Acute to chronic.

This report investigates an unusual case of recurrent pancreatitis. A 22-year-old female was admitted to the emergency room for severe abdominal pain, nausea, and weight loss. She reported having these symptoms since she was a toddler. The clinician ordered fecal pancreatic elastase-1, fat-soluble vitamins, molecular studies, and imaging of the pancreas by computed tomography. The screening test result for fecal pancreatic elastase-1 revealed severe pancreatic exocrine insufficiency, and the concentrations of fat-soluble vitamins were also low. Imaging showed scattered calcifications in the pancreas. These findings supported a diagnosis of chronic pancreatitis. Due to the rarity of chronic pancreatitis in young adults, molecular studies were performed. The patient was found to be homozygous for a mutation in the SPINK1 gene, which is associated with hereditary pancreatitis. This case report discusses hereditary pancreatitis and highlights data on the utilization of fecal pancreatic elastase-1 to assess pancreatic exocrine insufficiency.

Clinically Used Hormone Formulations Differentially Impact Memory, Anxiety-Like, and Depressive-Like Behaviors in a Rat Model of Transitional Menopause.

A variety of U.S. Food and Drug Administration-approved hormone therapy options are currently used to successfully alleviate unwanted symptoms associated with the changing endogenous hormonal milieu that occurs in midlife with menopause. Depending on the primary indication for treatment, different hormone therapy formulations are utilized, including estrogen-only, progestogen-only, or combined estrogen plus progestogen options. There is little known about how these formulations, or their unique pharmacodynamics, impact neurobiological processes. Seemingly disparate pre-clinical and clinical findings regarding the cognitive effects of hormone therapies, such as the negative effects associated with conjugated equine estrogens and medroxyprogesterone acetate vs. naturally circulating 17ß-estradiol (E2) and progesterone, signal a critical need to further investigate the neuro-cognitive impact of hormone therapy formulations. Here, utilizing a rat model of transitional menopause, we administered either E2, progesterone, levonorgestrel, or combinations of E2 with progesterone or with levonorgestrel daily to follicle-depleted, middle-aged rats. A battery of assessments, including spatial memory, anxiety-like behaviors, and depressive-like behaviors, as well as endocrine status and ovarian follicle complement, were evaluated. Results indicate divergent outcomes for memory, anxiety, and depression, as well as unique physiological profiles, that were dependent upon the hormone regimen administered. Overall, the combination hormone treatments had the most consistently favorable profile for the domains evaluated in rats that had undergone experimentally induced transitional menopause and remained ovary-intact. The collective results underscore the importance of investigating variations in hormone therapy formulation as well as the menopause background upon which these formulations are delivered.