Miracle-dz/UniFAR-FTUs huggingface dataset:
The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus

The aim of this paper is to review the information on type 1 and type 2 diabetes with emphasis on its etiology, pathogenesis and pathophysiology via literature review. Diabetes is a group of metabolic disorders characterized by a chronic hyperglycemic condition resulting from defects in insulin secretion, insulin action or both. Type 1 diabetes is the result of an autoimmune reaction to proteins of the islets cells of the pancreas while type 2 diabetes is caused by a combination of genetic factors related to impaired insulin secretion, insulin resistance and environmental factors such as obesity, overeating, lack of exercise and stress, as well as aging. The pathogenesis of selective β-cell destruction within the islet in type 1 diabetes mellitus is difficult to follow due to marked heterogeneity of the pancreatic lesions. At the onset of overt hyperglycemia, a mixture of pseudoatrophic islets with cells producing glycogen, somatostatin and pancreatic polypeptide, normal islets and islets containing both β-cells and infiltrating lymphocytes and monocytes may be seen. The autoimmune destruction of pancreatic β cells leads to a deficiency of insulin secretion that leads to the metabolic derangements associated with type 1 diabetes. The main pathophysiological features of type 2 diabetes are impaired insulin secretion and increased insulin resistance. The impairment of pancreatic β cell function notably shows progression overtime in type 2 diabetes although aging, obesity, insufficient energy consumption, alcohol drinking, smoking, etc are independent risk factors of pathogenesis of type 2 diabetes mellitus. Key words: Diabetes Mellitus, Pathophysiology, Pathogenesis, Etiology.
Primary Care in Australia

The Australian health care delivery system is reviewed in this article, with special comment on the implications of the financial components of the system and government concerns regarding costs and over-servicing. General practitioners' perception of their role is not significantly different from the expectation of patients, yet the reality may not match the idealized view. There are problems related to availability and there are developments which seem to pose some threat to the continuing care of patients. New developments have occurred in the way in which practice is organized which give an emphasis to continual availability over 24 hour periods, and these developments pose a challenge to the way in which doctors have organized their practices. Population features-Aborigines, migrants, and the elderly-present significant problems that are not always well met, and the concept of total patient care thereby suffers. The general practitioner's apparent failure to fill the expected role in co-ordination of services is discussed, as is the need for general practitioners to become more actively involved in health education and promotion. The hope for the future lies in the Family Medicine Programme of The Royal Australian College of General Practitioners, which represents a major attempt to provide appropriate vocational training for general practice.
QTc Prolongation in Acute Pediatric Migraine

Objectives Migraine headache is common in pediatrics and is frequently assessed in emergency departments. Altered cardiac conduction, including prolongation of the QTc interval on electrocardiogram, has been observed in adults during migraine headache and resolves interictally. Prolonged QTc is associated with life-threatening arrhythmia, and many acute and prophylactic therapies for migraine can further prolong the QTc interval. It is the objective of this prospective cohort study to examine whether the QTc interval prolongs significantly during periods of acute migraine headache in children. Methods Patients ages 6 to 17 years presenting to the emergency department with acute migraine headache were recruited prospectively. Exclusion criteria included the use of QTc-prolonging medications and medical illnesses, including cardiovascular abnormalities, infection, or head injury. Paired, one-tailed Student t tests compared QTc intervals with and without headache and evaluated for QTc prolongation of 30 ms or longer during headache. Results Thirteen patients with migraine (mean age, 11.6 ± 2.6 years) were evaluated. Mean QTc interval during headache was significantly longer than the QTc interval in the absence of headache (437.9 ± 27.7 ms compared with 419.3 ± 29.9 ms; p = 0.04). Three patients (23%) had unequivocal prolongation of the QTc (>460 ms) during the migraine, two of which normalized with headache resolution. The mean increase in QTc during headache did not reach or exceed 30 ms (p = 0.86) Conclusions This study is the first to illustrate a connection between QTc prolongation and acute migraine headache in children. If confirmed in future studies, children should be monitored for QTc prolongation during the acute treatment of migraine in the emergency department when using medications that can lengthen the QTc interval.
To the Hospital and Back Home Again: A Nurse Practitioner‐Based Transitional Care Program for Hospitalized Homebound People

Homebound older adults may receive suboptimal care during hospitalizations and transitions home or to postacute settings. This 2‐year study describes a nurse practitioner (NP)‐led transitional care program embedded within an existing home‐based primary care (HBPC) program. The transitional care pilot program was designed to improve coordination and continuity of care, reduce readmissions, garner positive provider feedback, and demonstrate financial benefits through shorter length of stay, lower cost of inpatient stay, and better documentation of patient complexity. A detailed mixed‐methods evaluation was conducted to characterize the hospitalized homebound population and investigate provider feedback and program feasibility, effectiveness, and costs. Length of stay (LOS), case‐mix index, and admission‐related financial costs were compared before and after the intervention using a pre–post design. Structured focus groups were conducted with inpatient and primary care providers to collect feedback on the usefulness of and satisfaction with the program. The program improved communication between home‐based primary care providers and inpatient providers of all disciplines and facilitated the timely and accurate transfer of critical patient information. The intervention failed to decrease hospital LOS and readmission rate significantly for people who were hospitalized. The financial implications were reassuring, although future studies are necessary. This model of a NP‐led program may be feasible for enhancing inpatient management and transitional care for older adults in HBPC programs and should be considered to augment the HBPC care model.
Earnings management and corporate governance related to mandatory IFRS adoption: evidence from French-listed firms

This study investigates how mandatory adoption of the new accounting standards and enforcement mechanisms such as Big 4 auditors and board independence influence earnings management. Based on a sample of 120 firms listed on the French stock exchange, we find that the mandatory adoption of IFRS does not affect managerial opportunism. In contrast with previous studies, our results show that the corporate governance mechanisms are not sufficiently strong to enforce the application of the IFRS standards in France. This can be due to the special characteristics of the French context known by the weak investors' protection rights even in the post–IFRS period. IFRS can be of high quality just if they are accompanied with some factors like efficient governance mechanisms and appropriate enforcement.
Exercise Training Increases Glucose Transporter Content in Skeletal Muscles More Efficiently From Aged Obese Rats Than Young Lean Rats

Glucose uptake in rat skeletal muscles decreases with age and obesity, but increases with chronic exercise training. The purpose of our study was to determine whether the GLUT4 content in several skeletal muscles from 1-mo-old young, lean rats and 12-mo-old aged, obese rats alters with exercise training. For exercise, a treadmill run of ∼ 1 km/day was made for 4 wk by both groups of rats. The concentration of GLUT4 per protein in membrane fraction from several skeletal muscles was measured by immunoblotting. The amount of GLUT4 in the gastrocnemius and white quadriceps from aged rats slightly but significantly decreased to 73% and 78% of that from young rats, respectively. However, no significant difference in GLUT4 amount in the soleus, plantaris, and red quadriceps was observed between young and aged rats. The exercise training resulted in a larger increase in the amount of GLUT4 in each muscle from aged rats than in muscles from young rats. In aged rats, GLUT4 amount increased significantly with exercise training by 30, 33, 41, and 27% in the soleus, plantaris, gastrocnemius, and red quadriceps, respectively, compared with the sedentary controls. However, in young rats, exercise-induced increase of GLUT4 amount was significant only in the plantaris, and the increase was 17%. In exercised aged, obese rats, decreases of body weight, plasma triglyceride levels, and plasma free fatty acid were also observed. These findings suggest that the amount of GLUT4 in some skeletal muscles decreases slightly in aged, obese rats, exercise training increases the amount of GLUT4 more efficiently in aged rats than in young rats and ameliorates the GLUT4 decrease observed in aged rats, and lipid metabolism may be related to the regulation of GLUT4 protein content in muscles.
Pyruvate Decarboxylase from Zea mays L. : I. Purification and Partial Characterization from Mature Kernels and Anaerobically Treated Roots.

Pyruvate decarboxylase (PDC) was purified from mature, dry maize kernels and from roots of anaerobically treated maize seedlings and partially characterized. PDC was purified to a specific activity of 96 units per milligram protein from kernels and to 41 units per milligram protein from root. The subunit molecular masses were estimated to be 61,000 and 60,000 for kernel PDC and 59,000 and 58,000 for root PDC. The pH optimum for each enzyme was 5.8. Since the pH optimum is nearly one pH unit below the value reported for the cytoplasm of anaerobically metabolizing maize roots (pH 6.7 +/- 0.2), we investigated the effects of pH 5.8 and 6.6 on the cooperative kinetics observed for PDC from each source. The maximum Hill coefficients (n(H)) were much greater at each pH for the kernel PDC (pH 5.8, n(H) = 2.5 and pH 6.6, n(H) = 3.2) than for the root PDC (pH 5.8, n(H) = 1.4 and pH 6.6, n(H) = 1.8). The cooperative kinetics observed with respect to pyruvate were asymmetric. Potassium inhibited maize PDC and was competitive with pyruvate (root PDC K(i) = 16 millimolar and kernel PDC K(i) = 10 millimolar).
BioAggregate and iRoot BP Plus optimize the proliferation and mineralization ability of human dental pulp cells.

AIM To investigate the cytotoxicity of BioAggregate and iRoot BP Plus root canal sealer (iRoot BP Plus) to human dental pulp cells (hDPCs) and their effect on proliferation and mineralization of hDPCs and to compare their performance with that of mineral trioxide aggregate (MTA). METHODOLOGY Human dental pulp cells were seeded onto the prepared BioAggregate, iRoot BP Plus and MTA, respectively. Cell proliferation was assessed by CCK-8 cell proliferation kit on days 1, 3, 5 and 7. ALP activity was measured to evaluate the cell differentiation potential on days 1, 3, 5 and 7. The expression of odontoblastic differentiation-related genes (dentine phosphoprotein, dentine matrix protein-1 and osteocalcin) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Statistical tests used were one-way anova and post hoc Tukey's test. RESULTS The proliferation of hDPCs in the MTA group was suppressed throughout the culture period, whereas the BioAggregate group and the iRoot BP Plus group first significantly increased cell numbers on day 1 (P < 0.01) and then decreased on day 3 to day 7. ALP activity was enhanced in all the three groups from day 3, whilst iRoot BP Plus showed significantly higher ALP activity than MTA (P < 0.01). qRT-PCR indicated that both BioAggregate and iRoot BP Plus groups were associated with a higher upregulation of mineralization and odontoblastic differentiation-associated gene expressions as compared to MTA group (P < 0.05). CONCLUSIONS BioAggregate and iRoot BP Plus were nontoxic and able to induce mineralization and odontoblastic differentiation-associated gene expression in hDPCs.
Dependency of Premature Ventricular Contractions on Heart Rate and Circadian Rhythms during Childhood

The aim of the present study was to identify and quantify the rate dependence of premature ventricular contractions (PVC) during childhood. A 24-hour Holter recording was performed in 16 consecutive children, aged 22 days to 11 years (mean age 5.6 years), with frequent (>5,000/day), isolated monomorphic PVC. Those PVC were identified and the length of the preceding sinus cycle was measured. The values were ordered into 50-ms class intervals, and the percentage of PVC for each class was calculated and then analyzed by linear regression analysis. On the basis of the significance of the p value, and the positive or negative value of the slope, we identified a tachycardia-enhanced, a bradycardia-enhanced, and an indifferent pattern. Chronobiologic analysis was made by the cosinor method. All the patients had upper and lower limits of cycle length beyond which PVC disappeared. A tachycardia-enhanced pattern was present in 7 patients and an indifferent one in 9 patients. In the latter a second-degree polynomial correlation was systematically found. Children but not infants had a significant circadian variation in the frequency of PVC with a very variable time of highest incidence. In conclusion, it is possible to identify a circadian rhythm of PVC and a spontaneous trend between their incidence and the length of the preceding cardiac cycle in children.
Socializing the C-suite: why some big-box retailers are “greener” than others

Despite a considerable push by policy-makers to incentivize green business practices, take-up of environmental initiatives amongst North American retailers has been highly uneven. While some “big-box” retailers have launched ambitious environmental initiatives, others continue to conduct business as usual. This paper asks: why do some mega-retailers commit to ambitious environmental agendas while others in the same sector do not? And how can the answer to this question improve public policy? I investigate these questions using comparative case studies of four North American big-box retailers: Wal-Mart, Target, Costco and Kroger. My findings suggest that the socialization of senior executives through multi-stakeholder sustainability networks is the critical variable accounting for progressive environmental practices in some corporations and not others. This finding suggests that existing public policies that focus on making the business case for sustainability are based on incomplete assumptions about why companies “go green. ” It further suggests that socialization theory can help explain broader instances of corporate social responsibility and proposes that scholars in this field should devote more attention to the composition of socializing groups.
The PDZ‐scaffold protein INAD abolishes apparent store‐dependent regulation of the light‐activated cation channel TRP

In fly photoreceptor cells, light initiates a G protein‐coupled phospholipase Cβ‐dependent signaling cascade that results in the depolarization of the cell membrane, which is mediated by the cation channels TRP and TRPL. Together with phospholipase Cβ and an eye‐specific protein kinase C, TRP is tethered to the scaffolding protein INAD, which forms a multimolecular signaling complex. Divergent data from expressed TRP and studies from photoreceptor cells have brought up a controversy whether or not a capacitative calcium entry (CCE) mechanism is involved in the Drosophila phototransduction pathway. Our initial characterization of TRP from photoreceptors of Calliphora vicina supported the hypothesis of a CCE mechanism, as heterologously expressed TRP was stimulated after application of thapsigargin. The situation changed when the PDZ domain protein INAD was coexpressed with TRP. In cells coexpressing TRP and INAD, no calcium entry was detectable on application of store depletion protocols. Suppression of CCE by INAD was not observed when the described interaction was disrupted by mutations in TRP and INAD. Our data show that apparent activation of TRP by CCE is abolished by INAD. Within the complex, the proteins necessary for phototransduction mutually influence their activities. The results support the hypothesis of a store‐independent activation of TRP.
Nutzerzentrierte Gestaltung einer Applikation im Diabetes-Kontext

Zusammenfassung Typ-1-Diabetes stellt nicht nur gesamtgesellschaftlich ein großes Problem dar, sondern ist auch für einzelne Betroffene durch vielfältige Aufgaben und Regeln eine starke Belastung. Um Ursachen für Blutzuckerschwankungen zu erkennen, ist eine umfangreiche Dokumentation diabetesbezogener Werte, wie z.B. Blutzucker oder Mahlzeiten, nötig. Oft mangelt es Betroffenen an Motivation, diese Dokumentation kontinuierlich durchzuführen. Um Betroffene zu unterstützen und durch positive Anreize zur Dokumentation zu motivieren, wird der Prototyp einer Smartphone-Applikation vorgestellt. Unter Berücksichtigung des nutzerzentrierten Designs wurden aufbauend auf Erkenntnissen positiver Psychologie Konzepte für den Prototyp herausgearbeitet. Dieser wurde durch Experten und Typ-1-Diabetiker im Hinblick auf motivierende Elemente und Usability evaluiert. Es zeigt sich, dass Betroffene durch die Applikation sinnvoll im Umgang mit der Erkrankung unterstützt werden.
Cognitive function across the life course and the menopausal transition in a British birth cohort

Objective:Despite biological plausibility, relationships between menopause and cognitive function are inconsistent. We investigated whether menopause status and menopause age were associated with general cognitive ability, verbal memory, and visual search speed and concentration in a large cohort of women while considering vasomotor and psychological symptoms, previous childhood and adult measures of cognitive function, lifetime socioeconomic circumstances, educational attainment, lifestyle factors, and chronic diseases. Design:A nationally representative British cohort of 1261 women born in March 1946 and all aged 53 years at cognitive testing, with prospective information on previous cognitive function, menopausal characteristics, and potential confounders. Results:There was only weak evidence of the effect of natural menopause on cognitive function and no evidence of any effects of hormone therapy use or hysterectomy status. There was a trend across the phases of the natural menopausal transition (pre-, peri-, and postmenopause) for the National Adult Reading Test (P = 0.005) and search speed and concentration (P = 0.042), with postmenopausal women having the lowest cognitive function, but there was no trend in verbal memory. Variation in vasomotor and psychological symptoms did not explain these trends. In postmenopausal women, there was a positive trend across menopause age for verbal memory (P = 0.004) and a weak positive trend for the National Adult Reading Test (P = 0.052), with women who reached menopause later having higher cognitive function. Previous cognitive function generally explained the associations, which were further weakened by adjusting for socioeconomic and educational confounders. One exception was the association between the natural menopause transition and search speed and concentration, which remained after adjustment for these factors. Conclusion:Menopause adversely affects cognitive function, but this effect may be largely explained by premenopausal cognitive function. These findings suggest that common environmental or genetic factors, operating through long-term or lifelong hormonal mechanisms, may influence the timing of natural menopause and lifetime cognitive function.
Guide RNAs for transcripts with developmentally regulated RNA editing are present in both life cycle stages of Trypanosoma brucei

RNA editing of several mitochondrial transcripts in Trypanosoma brucei is developmentally regulated. The cytochrome b and cytochrome oxidase II mRNAs are edited in procyclic-form parasites but are primarily unedited in bloodstream forms. The latter forms lack the mitochondrial respiratory system present in procyclic forms. Editing of the NADH dehydrogenase 7 (ND7) and ND8 transcripts is also developmentally regulated but occurs preferentially in bloodstream forms. Other transcripts, cytochrome oxidase III and ATPase 6, are edited in both life forms. We have identified many minicircle-encoded guide RNAs (gRNAs) for ATPase 6, ND7, and ND8. The characteristics of these gRNAs reveal how extensively edited RNA can be edited in the 3'-to-5' direction. Northern (RNA) blot and primer extension analyses indicate that gRNAs for transcripts whose editing is developmentally regulated are present in both procyclic and bloodstream form parasites. These results suggest that the developmental regulation of editing in these transcripts is not controlled by the presence or absence of gRNAs.
Role of Premature Stop Codons in Bacterial Evolution

ABSTRACT When the stop codons TGA, TAA, and TAG are found in the second and third reading frames of a protein-encoding gene, they are considered premature stop codons (PSC). Deinococcus radiodurans disproportionately favored TGA more than the other two triplets as a PSC. The TGA triplet was also found more often in noncoding regions and as a stop codon, though the bias was less pronounced. We investigated this phenomenon in 72 bacterial species with widely differing chromosomal GC contents. Although TGA and TAG were compositionally similar, we found a great variation in use of TGA but a very limited range of use of TAG. The frequency of use of TGA in the gene sequences generally increased with the GC content of the chromosome, while the frequency of use of TAG, like that of TAA, was inversely proportional to the GC content of the chromosome. The patterns of use of TAA, TGA and TAG as real stop codons were less biased and less influenced by the GC content of the chromosome. Bacteria with higher chromosomal GC contents often contained fewer PSC trimers in their genes. Phylogenetically related bacteria often exhibited similar PSC ratios. In addition, metabolically versatile bacteria have significantly fewer PSC trimers in their genes. The bias toward TGA but against TAG as a PSC could not be explained either by the preferential usage of specific codons or by the GC contents of individual chromosomes. We proposed that the quantity and the quality of the PSC in the genome might be important in bacterial evolution.
Toward an Understanding of Causality Between Advertising and Sales: New Evidence from a Multivariate Cointegrated System

This article explores the nature of causality between advertising and sales for two mature brands in different industries (carbonated soft drinks and smokeless tobacco) using more than three decades of time series data. The empirical results suggest that advertising and sales for both brands move in tandem over the long term, but only when controlling for economic climate. The results further imply that for Brand CSD (carbonated soft drinks), advertising and sales appear causally unrelated in the short run, while significant one-way causality exists from sales to advertising in the long run. This suggests that advertising investments over the long term are dependent on sales revenues, opposite to what is commonly perceived. A similar advertising policy may be in place over the short term for Brand T (tobacco). The analysis extends prior research by revisiting the “advertising or sales” assessment using current data from mature industries. We contend that advertising expenditures are subject to change based on sales volume in slow-growth industries.