Basolateral Junction Proteins Regulate Competition for the Follicle Stem Cell Niche in the Drosophila Ovary

Epithelial stem cells are routinely lost or damaged during adult life and must therefore be replaced to maintain homeostasis. Recent studies indicate that stem cell replacement occurs through neutral competition in many types of epithelial tissues, but little is known about the factors that determine competitive outcome. The epithelial follicle stem cells (FSCs) in the Drosophila ovary are regularly lost and replaced during normal homeostasis, and we show that FSC replacement conforms to a model of neutral competition. In addition, we found that FSCs mutant for the basolateral junction genes, lethal giant larvae (lgl) or discs large (dlg), undergo a biased competition for niche occupancy characterized by increased invasion of neighboring FSCs and reduced loss. Interestingly, FSCs mutant for a third basolateral junction gene, scribble (scrib), do not exhibit biased competition, suggesting that Lgl and Dlg regulate niche competition through a Scrib-independent process. Lastly, we found that FSCs have a unique cell polarity characterized by broadly distributed adherens junctions and the lack of a mature apical domain. Collectively, these observations indicate that Lgl and Dlg promote the differentiation of FSC progeny to a state in which they are less prone to invade the neighboring niche. In addition, we demonstrate that the neutral drift model can be adapted to quantify non-neutral behavior of mutant clones

Share of afghanistan populace in hepatitis B and hepatitis C infection's pool: is it worthwhile?

There is a notable dearth of data about Hepatitis B Virus (HBV) and Hepatitis C Virus(HCV) prevalence in Afghanistan. Awareness program and research capacity in the field of hepatitis are very limited in Afghanistan. Number of vulnerabilities and patterns of risk behaviors signal the need to take action now

Bridging the Gap: Selected Works and TopScholar Galleries

Higher education’s scholars utilize online catalogs and library finding aids with ease. However, for the larger community, accessing scholars’ Selected Works and online galleries with topical themes is a helpful intermediary step. Non-scholars often explore and produce scholarship, seek out obscure online sources and gladly volunteer to document cultural resources.Every day historically valuable ephemera is thrown away due to an ignorance of its value to research. Special Collections Librarians partnering with Scholarly Communication Specialists utilize social media to create a gateway and make certain that taxpaying interested parties do not miss the wealth of primary sources compiled over centuries by librarians and archivists. We hope this ease of access to information will encourage casual researchers to support our academic efforts. It may also result in donations of unique letters, photographs, diaries, ephemera and inaccessible publications. The Special Collections galleries allow exhibits of unique photographs, ephemera, oral histories and manuscripts. Scholars create personal selected works sites to showcase individual research projects and collections. University faculty, teachers, adults, and amateur historians can use these accessible resources to gather information and create items to motivate, entertain or educate others. Technology created the door to Libraries via KenCat and TopScholar. Now the galleries and Selected Works throw open wide resources for all

Cardiorespiratory Responses during Aquatic Treadmill Exercise and Land Treadmill Exercise in Adults with Diabetes

The purpose of this study was to compare the effect of aquatic treadmill (ATM) exercise to land treadmill (LTM) exercise in adults with type 2 diabetes. Five participants with type 2 diabetes (T2D group; 4 females, 1 male; age = 51±6 years; height = 170±7 cm; weight = 96±24 kg; body fat = 31.6±2.2%) and five participants without type 2 diabetes (control group; 4 females, 1 male; age = 51±6 years; height = 170±6 cm; weight = 71±15 kg; body fat = 26.8±4.6%) completed the study. Protocols for both ATM exercise and LTM exercise began at 2 mph with 0% grade and increased by 1 mph after 5 minutes at each stage. Termination occurred after participants completed the protocol or reached 85% of heart rate reserve. Heart rate, absolute and relative VO2, and systolic and diastolic blood pressure were measured at rest and during steady-state exercise at each intensity. Mean arterial pressure (MAP) was calculated. A 2 x 2 x 3 Mixed Factorial ANOVA and Bonferroni post hoc test with a significance level of .0125 were used. There was a significant difference (p2 of the two groups at 4 mph while performing the land treadmill exercise (T2D: 14.1±1.4 ml/kg/min vs. control: 18.4±1.6 ml/kg/min, p2 between participant groups or modes of exercise. Those with type 2 diabetes had an increased MAP versus those without type 2 diabetes while performing the land treadmill exercise at 2 mph (T2D: 93±3 mmHg vs. control: 81±5 mmHg, p2, and MAP respond similarly in both groups during ATM and LTM exercise at most treadmill speeds

Antibodies to the Mr 64,000 (64K) protein in islet cell antibody positive non-diabetic individuals indicate high risk for impaired Beta-cell function

A prospective study of a normal childhood population identified 44 islet cell antibody positive individuals. These subjects were typed for HLA DR and DQ alleles and investigated for the presence of antibodies to the Mr 64,000 (64K) islet cell antigen, complement-fixing islet cell antibodies and radiobinding insulin autoantibodies to determine their potency in detecting subjects with impaired Beta-cell function. At initial testing 64K antibodies were found in six of 44 islet cell antibody positive subjects (13.6%). The same sera were also positive for complement-fixing islet cell antibodies and five of them had insulin autoantibodies. During the follow-up at 18 months, islet cell antibodies remained detectable in 50% of the subjects studied. In all six cases who were originally positive, 64K antibodies were persistently detectable, whereas complement-fixing islet cell antibodies became negative in two of six and insulin autoantibodies in one of five individuals. HLA DR4 (p < 0.005) and absence of asparic acid (Asp) at position 57 of the HLA DQ chain (p < 0.05) were significantly increased in subjects with 64K antibodies compared with control subjects. Of 40 individuals tested in the intravenous glucose tolerance test, three had a first phase insulin response below the first percentile of normal control subjects. Two children developed Type 1 (insulin-dependent) diabetes mellitus after 18 and 26 months, respectively. Each of these subjects was non-Asp homozygous and had persistent islet cell and 64K antibodies. We conclude that 64K antibodies, complement-fixing islet cell antibodies and insulin autoantibodies represent sensitive serological markers in assessing high risk for a progression to Type 1 diabetes in islet cell antibody positive non-diabetic individuals

The Dose Effect of Whey Protein on Insulin Responses in Pre-Diabetics and Type 2 Diabetics

People with pre-diabetes and type 2 diabetes have shown an increase in insulin secretion after ingesting 55 g of whey protein coupled with a glycemic challenge. However, the effect of lower amounts of whey protein on insulin responses remains unclear. Our hypothesis was that both 20 g and 30 g of whey consumption prior to an oral glucose tolerance test (OGTT) would produce an increase in insulin secretion, with 30 g producing the greatest increase compared to a control. PURPOSE: The purpose of this study was to examine the effect of two different doses of whey protein ingested 30 min prior to a 50 g OGTT on glucose, insulin, C-peptide, and glucagon responses. METHODS: Diabetic or pre-diabetic participants (n=9, mean ± SD; age: 64.3 + 8.1 yrs; BMI: 29.4 + 6.0 kg/m2; body fat percentage: 42.5 + 7.8 %; fasting plasma glucose: 6.9 + 1.2 mmol/l; HbA1c: 6.4 + 0.6 %) completed three trials. The randomly assigned trials consisted of: 250 ml of water (CON), 250 ml of water + 20 g whey (20g), and 250 ml of water + 30 g whey (30g), followed by an OGTT. Blood was collected at -30, 0, 15, 30, 60, 90, 120, and 150 min for the measurement of glucose, insulin, C-peptide, and glucagon. The whey protein mixture was administered immediately following the -30 min blood draw, and the 50 g OGTT began immediately following the 0 min blood draw. Glucose was analyzed using a YSI 2900D glucose analyzer and insulin, C-peptide, and glucagon were measured via multiplex fluorescent detection (MagPix). A one-way repeated measures ANOVA (pRESULTS: Incremental area under the curve (AUC) for glucose presented no difference between the 3 trials. Insulin AUC was significantly increased from CON to 20g (p=0.004, 36.3%), CON to 30g (p=0.002, 61.7%), and 20g to 30g (p=0.030, 18.6%). C-peptide and glucagon AUC significantly increased from CON to 20g (p=0.018, 20.6%; p=0.046, 33.1%) and CON to 30g (p=0.001, 30.1%; p=0.017, 33.7%). CONCLUSION: Whey protein elicited a dose response on plasma insulin, increasing concentrations from CON to 20g, and 20g to 30g, however plasma glucose was unaffected. 20g and 30g displayed similar responses for glucagon. Neither 20 g nor 30 g of whey protein may be adequate to provide glycemic improvement in the disease management of type 2 or pre-diabetes

External Bone Size Is a Key Determinant of Strength‐Decline Trajectories of Aging Male Radii

Given prior work showing associations between remodeling and external bone size, we tested the hypothesis that wide bones would show a greater negative correlation between whole‐bone strength and age compared with narrow bones. Cadaveric male radii (n = 37 pairs, 18 to 89 years old) were evaluated biomechanically, and samples were sorted into narrow and wide subgroups using height‐adjusted robustness (total area/bone length). Strength was 54% greater (p < 0.0001) in wide compared with narrow radii for young adults (<40 years old). However, the greater strength of young‐adult wide radii was not observed for older wide radii, as the wide (R2 = 0.565, p = 0.001), but not narrow (R2 = 0.0004, p = 0.944) subgroup showed a significant negative correlation between strength and age. Significant positive correlations between age and robustness (R2 = 0.269, p = 0.048), cortical area (Ct.Ar; R2 = 0.356, p = 0.019), and the mineral/matrix ratio (MMR; R2 = 0.293, p = 0.037) were observed for narrow, but not wide radii (robustness: R2 = 0.015, p = 0.217; Ct.Ar: R2 = 0.095, p = 0.245; MMR: R2 = 0.086, p = 0.271). Porosity increased with age for the narrow (R2 = 0.556, p = 0.001) and wide (R2 = 0.321, p = 0.022) subgroups. The wide subgroup (p < 0.0001) showed a significantly greater elevation of a new measure called the Cortical Pore Score, which quantifies the cumulative effect of pore size and location, indicating that porosity had a more deleterious effect on strength for wide compared with narrow radii. Thus, the divergent strength–age regressions implied that narrow radii maintained a low strength with aging by increasing external size and mineral content to mechanically offset increases in porosity. In contrast, the significant negative strength–age correlation for wide radii implied that the deleterious effect of greater porosity further from the centroid was not offset by changes in outer bone size or mineral content. Thus, the low strength of elderly male radii arose through different biomechanical mechanisms. Consideration of different strength–age regressions (trajectories) may inform clinical decisions on how best to treat individuals to reduce fracture risk. © 2019 American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149566/1/jbmr3661_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149566/2/jbmr3661.pd

Airway resistance at maximum inhalation as a marker of asthma and airway hyperresponsiveness

<p>Abstract</p> <p>Background</p> <p>Asthmatics exhibit reduced airway dilation at maximal inspiration, likely due to structural differences in airway walls and/or functional differences in airway smooth muscle, factors that may also increase airway responsiveness to bronchoconstricting stimuli. The goal of this study was to test the hypothesis that the minimal airway resistance achievable during a maximal inspiration (R_min) is abnormally elevated in subjects with airway hyperresponsiveness.</p> <p>Methods</p> <p>The R_minwas measured in 34 nonasthmatic and 35 asthmatic subjects using forced oscillations at 8 Hz. R_minand spirometric indices were measured before and after bronchodilation (albuterol) and bronchoconstriction (methacholine). A preliminary study of 84 healthy subjects first established height dependence of baseline R_minvalues.</p> <p>Results</p> <p>Asthmatics had a higher baseline R_min% predicted than nonasthmatic subjects (134 ± 33 vs. 109 ± 19 % predicted, p = 0.0004). Sensitivity-specificity analysis using receiver operating characteristic curves indicated that baseline R_minwas able to identify subjects with airway hyperresponsiveness (PC₂₀< 16 mg/mL) better than most spirometric indices (Area under curve = 0.85, 0.78, and 0.87 for R_min% predicted, FEV₁% predicted, and FEF_25-75% predicted, respectively). Also, 80% of the subjects with baseline R_min< 100% predicted did not have airway hyperresponsiveness while 100% of subjects with R_min> 145% predicted had hyperresponsive airways, regardless of clinical classification as asthmatic or nonasthmatic.</p> <p>Conclusions</p> <p>These findings suggest that baseline R_min, a measurement that is easier to perform than spirometry, performs as well as or better than standard spirometric indices in distinguishing subjects with airway hyperresponsiveness from those without hyperresponsive airways. The relationship of baseline R_minto asthma and airway hyperresponsiveness likely reflects a causal relation between conditions that stiffen airway walls and hyperresponsiveness. In conjunction with symptom history, R_mincould provide a clinically useful tool for assessing asthma and monitoring response to treatment.</p

The validity of using ICD-9 codes and pharmacy records to identify patients with chronic obstructive pulmonary disease

Background: Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear. We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD. Methods: Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007). COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal. Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry. Model performance was assessed using standard criteria. Results: 4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70. The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76). Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78). The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80). Conclusion: Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD. Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.Department of Veterans Affairs, Health Services Research and Development (DHA), American Lung Association (CI- 51755-N) awarded to DHA, the American Thoracic Society Fellow Career Development AwardPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84155/1/Cooke - ICD9 validity in COPD.pd

Reduced level of arousal and increased mortality in adult acute medical admissions: a systematic review and meta-analysis

Abstract Background Reduced level of arousal is commonly observed in medical admissions and may predict in-hospital mortality. Delirium and reduced level of arousal are closely related. We systematically reviewed and conducted a meta-analysis of studies in adult acute medical patients of the relationship between reduced level of arousal on admission and in-hospital mortality. Methods We conducted a systematic review (PROSPERO: CRD42016022048), searching MEDLINE and EMBASE. We included studies of adult patients admitted with acute medical illness with level of arousal assessed on admission and mortality rates reported. We performed meta-analysis using a random effects model. Results From 23,941 studies we included 21 with 14 included in the meta-analysis. Mean age range was 33.4 - 83.8 years. Studies considered unselected general medical admissions (8 studies, n=13,039) or specific medical conditions (13 studies, n=38,882). Methods of evaluating level of arousal varied. The prevalence of reduced level of arousal was 3.1%-76.9% (median 13.5%). Mortality rates were 1.7%-58% (median 15.9%). Reduced level of arousal was associated with higher in-hospital mortality (pooled OR 5.71; 95% CI 4.21-7.74; low quality evidence: high risk of bias, clinical heterogeneity and possible publication bias). Conclusions Reduced level of arousal on hospital admission may be a strong predictor of in-hospital mortality. Most evidence was of low quality. Reduced level of arousal is highly specific to delirium, better formal detection of hypoactive delirium and implementation of care pathways may improve outcomes. Future studies to assess the impact of interventions on in-hospital mortality should use validated assessments of both level of arousal and delirium