Miracle-dz/UniFAR-FTUs huggingface dataset:
BULLIS FEVER (Lone Star Fever—Tick Fever): AN ENDEMIC DISEASE OBSERVED AT BROOKE GENERAL HOSPITAL, FORT SAM HOUSTON, TEXAS

During the spring and summer of 1942 many patients suffering from various acute febrile diseases were admitted to the contagious disease section of Brooke General Hospital, Fort Sam Houston, Texas. Most of these illnesses presented no great diagnostic problem, being recognized as seasonal diseases, such as infections of the upper respiratory tract, tonsillitis and mild influenza. In April it became apparent that in this group of patients we were confronted with a number of acutely ill ones who were suffering from a clinical disease entity which had defied definite identification. A search of the available literature failed to throw any light on this perplexing problem, and no reportof similar cases could be found. There were several outstanding clinical features characteristic of this disease, i. e. an unusually low white blood cell count with moderate neutropenia, a severe postorbital and occipital headache, and a constant lymphadenitis varying from involvement of a
Multiple Mechanisms for Accumulation of Myosin II Filaments at the Equator During Cytokinesis

Total internal reflection fluorescence microscopy revealed how individual bipolar myosin II filaments accumulate at the equatorial region in dividing Dictyostelium cells. Direct observation of individual filaments in live cells provided us with much convincing information. Myosin II filaments accumulated at the equatorial region by at least two independent mechanisms: (i) cortical flow, which is driven by myosin II motor activities and (ii) de novo association to the equatorial cortex. These two mechanisms were mutually redundant. At the same time, myosin II filaments underwent rapid turnover, repeating their association and dissociation with the actin cortex. Examination of the lifetime of mutant myosin filaments in the cortex revealed that the turnover mainly depended on heavy chain phosphorylation and that myosin motor activity accelerated the turnover. Double mutant myosin II deficient in both motor and phosphorylation still accumulated at the equatorial region, although they displayed no cortical flow and considerably slow turnover. Under this condition, the filaments stayed for a significantly longer time at the equatorial region than at the polar regions, indicating that there are still other mechanisms for myosin II accumulation such as binding partners or stabilizing activity of filaments in the equatorial cortex.
The relationship between interleukin‐1 receptor antagonist and cognitive function in older adults with bipolar disorder

Cognitive impairments are a feature of bipolar disorder (BD) and could be worsened by inflammatory cytokines. We determined whether (i) serum interleukin‐1 receptor antagonist (IL‐1RA) was increased in elderly BD subjects; (ii) whether IL‐1RA was associated with worse neurocognitive function; and (iii) whether IL‐1RA was associated with white matter integrity.
Phosphodiesterase-5 inhibitors and benign prostatic hyperplasia

Purpose of review Benign prostatic hyperplasia (BPH) is prevalent in old men and often results in lower urinary tract symptoms (LUTS). Phosphodiesterase-5 (PDE5) inhibitors increase intracellular concentrations of cyclic guanosine monophosphate. PDE5 inhibitors (sildenafil, tadalafil, vardenafil, etc.) are first-line treatments for erectile dysfunction. Recently, PDE5 inhibitors have been found to regulate smooth muscle tone in human prostate. This article focuses on the use of PDE5 inhibitors for BPH/LUTS treatment and highlights the clinical significance. Recent findings Preclinical and clinical studies have provided promising evidence that PDE5 inhibitors may be an effective and well tolerated treatment option for BPH/LUTS. Combination therapy using PDE5 inhibitors and α1-adrenergic blockers resulted in greater improvements in BPH/LUTS than did either drug alone. Summary There has been increasing interest in the use of PDE5 inhibitors to treat BPH/LUTS. Combination of PDE5 inhibitors and α1-adrenergic blockers may have an additive beneficial effect on BPH/LUTS compared with monotherapy. Mechanisms of action of nitric oxide/cyclic guanosine monophosphate/PDE5 pathway in the treatment of BPH/LUTS deserve further investigations. Larger-scale, well designed clinical trials in future are needed to ascertain the safety, efficacy and cost-effectiveness of PDE5 inhibitors in the treatment of LUTS secondary to BPH.
Intracellular Assembly and Trafficking of MHC Class I Molecules

The presentation of antigenic peptides by class I molecules of the major histocompatibility complex begins in the endoplasmic reticulum (ER) where the co‐ordinated action of molecular chaperones, folding enzymes and class I‐specific factors ensures that class I molecules are loaded with high‐affinity peptide ligands that will survive prolonged display at the cell surface. Once assembled, class I molecules are released from the quality‐control machinery of the ER for export to the plasma membrane where they undergo dynamic endocytic cycling and turnover. We review recent progress in our understanding of class I assembly, anterograde transport and endocytosis and highlight some of the events targeted by viruses as a means to evade detection by cytotoxic T cells and natural killer cells.
Estrogens and phytoestrogens in male infertility

Purpose of review A time-related negative trend in male reproductive function has been suggested. It has been hypothesized that this is due to exposure to chemicals interfering with the action of sex hormones. Also a negative effect of phytoestrogens on male fertility has been postulated. This review aimed to review the epidemiological evidence of deteriorating male reproductive function and summarize the most recent literature on exposure to endocrine disrupters and phytoestrogens in relation to male fertility and/or semen quality. Recent findings There is no doubt that the incidence of testicular cancer has increased through the past 50 years, a decline in sperm counts, if any, may have leveled off during the past decade. There are some reports indicating negative association between exposure to certain chemicals and sperm parameters such evidence has not been found for phytoestrogens. The majority of these studies have been limited to assessing postnatal exposure. Summary Although possible negative impact of industrial chemicals and male fertility is an important issue on the research agenda, so far, it has no clinical implications. The future research should focus on looking at the impact of low dose exposure to a mixture of chemicals, two generation studies and gene-environment interaction.
Secretory Granule Membrane Protein Recycles through Multivesicular Bodies

The recycling of secretory granule membrane proteins that reach the plasma membrane following exocytosis is poorly understood. As a model, peptidylglycine α‐amidating monooxygenase (PAM), a granule membrane protein that catalyzes a final step in peptide processing was examined. Ultrastructural analysis of antibody internalized by PAM and surface biotinylation showed efficient return of plasma membrane PAM to secretory granules. Electron microscopy revealed the rapid movement of PAM from early endosomes to the limiting membranes of multivesicular bodies and then into intralumenal vesicles. Wheat germ agglutinin and PAM antibody internalized simultaneously were largely segregated when they reached multivesicular bodies. Mutation of basally phosphorylated residues (Thr946, Ser949) in the cytoplasmic domain of PAM to Asp (TS/DD) substantially slowed its entry into intralumenal vesicles. Mutation of the same sites to Ala (TS/AA) facilitated the entry of internalized PAM into intralumenal vesicles and its subsequent return to secretory granules. Entry of PAM into intralumenal vesicles is also associated with a juxtamembrane endoproteolytic cleavage that releases a 100‐kDa soluble PAM fragment that can be returned to secretory granules. Controlled entry into the intralumenal vesicles of multivesicular bodies plays a key role in the recycling of secretory granule membrane proteins.
Unraveling the Golgi Ribbon

The Golgi apparatus lies at the heart of the secretory pathway where it receives, modifies and sorts protein cargo to the proper intracellular or extracellular location. Although this secretory function is highly conserved throughout the eukaryotic kingdom, the structure of the Golgi complex is arranged very differently among species. In particular, Golgi membranes in vertebrate cells are integrated into a single compact entity termed the Golgi ribbon that is normally localized in the perinuclear area and in close vicinity to the centrosomes. This organization poses a challenge for cell division when the single Golgi ribbon needs to be partitioned into the two daughter cells. To ensure faithful inheritance in the progeny, the Golgi ribbon is divided in three consecutive steps in mitosis, namely disassembly, partitioning and reassembly. However, the structure of the Golgi ribbon is only present in higher animals and Golgi disassembly during mitosis is not ubiquitous in all organisms. Therefore, there must be unique reasons to build up the Golgi in this particular conformation and to preserve it over generations. In this review, we first highlight the diversity of the Golgi architecture in different organisms and revisit the concept of the Golgi ribbon. Following on, we discuss why the ribbon is needed and how it forms in vertebrate cells. Lastly, we conclude with likely purposes of mitotic ribbon disassembly and further propose mechanisms by which it regulates mitosis.
Should histologic variants alter definitive treatment of bladder cancer?

Purpose of review The clinical significance of variant histology is controversial and diagnosis is challenging. If variant architecture truly identifies high-risk patients, or those with a differential response to therapy, than treatment algorithms should be altered. This review outlines the current evidence and determines whether histologic variants should indeed alter definitive treatment. Recent findings For patients with pure squamous cell, adenocarcinoma, or small cell carcinoma, there is clear evidence to alter treatment paradigms. In adenocarcinoma or squamous cell carcinoma, there is a focus on local control and multimodal therapy with radiation. In small cell carcinoma all stages should be treated with primary chemotherapy followed by surgical extirpation. For patients with other variants of urothelial differentiation (i.e., micropapillary, sarcomatoid, squamous/glandular differentiation, etc.), management guidelines are less clear and radical cystectomy remains the mainstay of treatment at this time. Summary The management of variant histology is challenging as it not only depends on accurate diagnosis and staging, but on assumptions regarding sensitivity to multimodal therapy (i.e., chemotherapy, radiation, intravesical agents) based on a handful of retrospective case series. This will need to be the focus of future studies and collaborative efforts in order to make significant advancements in the field.
Regulation of β‐Catenin Nuclear Dynamics by GSK‐3β Involves a LEF‐1 Positive Feedback Loop

Nuclear localization of β‐catenin is integral to its role in Wnt signaling and cancer. Cellular stimulation by Wnt or lithium chloride (LiCl) inactivates glycogen synthase kinase‐3β (GSK‐3β), causing nuclear accumulation of β‐catenin and transactivation of genes that transform cells. β‐catenin is a shuttling protein; however, the mechanism by which GSK‐3β regulates β‐catenin nuclear dynamics is poorly understood. Here, fluorescence recovery after photobleaching assays were used to measure the β‐catenin‐green fluorescent protein dynamics in NIH 3T3 cells before and after GSK‐3β inhibition. We show for the first time that LiCl and Wnt3a cause a specific increase in β‐catenin nuclear retention in live cells and in fixed cells after detergent extraction. Moreover, LiCl reduced the rate of nuclear export but did not affect import, hence biasing β‐catenin transport toward the nucleus. Interestingly, the S45A mutation, which blocks β‐catenin phosphorylation by GSK‐3β, did not alter nuclear retention or transport, implying that GSK‐3β acts through an independent regulator. We compared five nuclear binding partners and identified LEF‐1 as the key mediator of Wnt3a and LiCl‐induced nuclear retention of β‐catenin. Thus, Wnt stimulation triggered a LEF‐1 positive feedback loop to enhance the nuclear chromatin‐retained pool of β‐catenin by 100–300%. These findings shed new light on regulation of β‐catenin nuclear dynamics.
Impact of Fructose Diet and Renal Failure on the Function of Pancreatic Islets

Objectives This study was designed to evaluate the impact of fructose-rich diet and chronic kidney disease (CKD) on the in vitro function of pancreatic islets. Methods Fifty-four rats were divided into 3 equal groups as follows: control, rats with CKD 1/2 that underwent surgical uninephrectomy, and rats with CKD 5/6 that underwent uninephrectomy and kidney cortex mass resection. Each group was further assigned to 3 diet protocols—regular diet, regular diet with 10% fructose (F10), and 60% fructose-rich diet (F60). After 8 weeks of insulin administration, C-peptide, glycated hemoglobin level, serum urea nitrogen, creatinine clearance, and homeostasis model assessment of insulin resistance were evaluated. Static glucose insulin stimulation test of isolated pancreatic islets and histologic analysis of pancreatic tissue were performed. Results The F10 diet increased the levels of insulin and C-peptide in all groups. Homeostasis model assessment of insulin resistance was increased in all animals fed with fructose. The elevated levels of creatinine and diminished creatinine clearance were detected in CKD 5/6 rats fed with 60% fructose-rich diet. The F10 diet resulted in high levels of serum insulin and C-peptide and glucose-stimulated insulin secretion. Fructose-rich diet increased the islet size and number, with irregular morphology and exocrine tissue fibrosis. Conclusions The fructose-rich diet accelerates the progression of CKD and affects the pancreatic islet function.
Educator Readiness to Adopt Expanded School Mental Health: Findings and Implications for Cross-Systems Approaches

Expanded school mental health (ESMH) professionals routinely partner with schools to provide ESMH services. An improved understanding of educators' perspectives in these partnerships is essential. In fact, these approaches often rely on educators as critical change agents. However, educators have traditionally received little training or preparation in children's mental health (Koller & Bertel, 2006). Existing research identifies the importance of readiness as a key construct for individuals' willingness to adopt innovations. Educators in Missouri (N = 89), Ohio (N = 32), and Kansas (N = 1) completed a 66-item online survey assessing readiness to adopt ESMH approaches, perceptions of stress, teaching self-efficacy, professional support, and students' mental health needs. Hierarchical regression analysis revealed that educator stress, perceptions of students' mental health needs, and teaching self-efficacy were all predictors of educators' readiness to adopt ESMH approaches. These findings could prove relevant to collaborative efforts across systems and help ESMH professionals understand the various factors related to educator readiness.
Chemical composition, antioxidant and antibacterial properties of Pteranthus dichotomus from Algerian Sahara

The phytochemical study of ethyl acetate and n-butanol extracts of Pteranthus dichotomus Forssk. led to the isolation and identification of 11 compounds, including three glycolipids 1–3, one lignan 4, three flavonoids 5–7 and four phytosterols 8–11. Structures of the isolated compounds have been elucidated by analysis of 1D and 2D NMR data, and mass spectrometry EI-MS and ESI-MS and by comparison with literature data. Furthermore, the ethyl acetate and n-butanol extracts were examined for their antioxidant and antibacterial activities. The results showed that both extracts (PDAC and PDBU) had a moderate antioxidant activity (IC50 = 375.514 μg/mL and 691.333 μg/mL) respectively.
The Role of EGF Receptor Ubiquitination in Regulating Its Intracellular Traffic

Progression of activated EGF receptor (EGFR) through the endocytic pathway regulates EGFR signaling. Here we show that a non‐ubiquitinated EGFR mutant, unable to bind the endosomal‐sorting complex required for transport (ESCRT) component, Hrs, is not efficiently targeted onto intraluminal vesicles (ILVs) of multivesicular endosomes/bodies (MVBs). Moreover, ubiquitination and ESCRT engagement of activated EGFR are required for EGF‐stimulated ILV formation. Non‐ubiquitinated EGFRs enter clathrin‐coated tubules emanating from MVBs and show enhanced recycling to the plasma membrane, compared to wild‐type EGFR.
Class II Transactivator-Induced MHC Class II Expression in Pancreatic Cancer Cells Leads to Tumor Rejection and a Specific Antitumor Memory Response

Objectives The loss of major histocompatibility complex (MHC) classes I and II is a well-known mechanism by which cancer cells are able to escape from immune recognition. In this study, we analyzed the expression of antigen processing and presenting molecules in 2 cell lines derived from mouse models of pancreatic ductal adenocarcinoma (PDA) and the effects of the re-expression of MHC class II on PDA rejection. Methods The PDA cell lines were analyzed for the expression of MHC class I, II, and antigen-processing molecules by flow cytometry or polymerase chain reaction. We generated stable PDA-MHC class II transactivator (CIITA) cells and injected them into syngeneic mice. The CD4 and CD8 T-cell role was analyzed in vitro and in vivo. Results Murine PDA cell lines were negative for MHC and antigen-processing molecules, but their expression was restored by exogenous interferon-&ggr;. CIITA-tumor cells were rejected in 80% to 100% of injected mice, which also developed long-lasting immune memory. In vitro assays and immunohistochemical analyses revealed the recruitment of T effector cells and CD8 T cells into the tumor area. Conclusions Overall, these data confirm that immunotherapy is a feasible therapeutic approach to recognize and target an aggressive cancer such as PDA.
Assessing the quality of physiotherapy services using Servqual

This paper continues to test the hypothesis as to the applicability of the Servqual model to the public sector. Research was undertaken using the model to assess the quality of three different types of physiotherapy service provision in Dundee, Scotland. The findings indicate that the services were much appreciated by patients in spite of the perceptions‐minus‐expectations scores being slightly negative. Information relating to patients’ conditions could be improved and, as has been found in previous similar healthcare research, the dimensions of assurance and empathy were highlighted as important. A critique of the Servqual model pinpoints and confirms certain weaknesses that need to be addressed but the study nonetheless confirms the potential usefulness and relevance of Servqual in the public sector context to determine consumer priorities and measure service performance.
Rosiglitazone Inhibits Hepatic Insulin Resistance Induced by Chronic Pancreatitis and IKK-&bgr;/NF-&kgr;B Expression in Liver

Objectives This study aimed to investigate the influence of rosiglitazone on hepatic insulin resistance and the expressions of I&kgr;B kinase-&bgr; (IKK-&bgr;)/nuclear factor-&kgr;B (NF-&kgr;B) in chronic pancreatitis (CP). Methods After CP was induced in rats, rosiglitazone and GW9662 were administered at the doses of 4 and 2 mg/kg per day for 4 weeks, respectively. Then, glucose and insulin tolerance tests were performed. Hepatocytes were isolated for the glucose release experiments. Determination of the IKK-&bgr;, NF-&kgr;B, and Ser307p-insulin receptor substrates-1 (Ser307p-IRS-1) expression in the liver was performed. Results The increased plasma glucose, reduced insulin sensitivity, and the capacity of insulin to suppress glucose release in hepatocytes were observed in CP rats. The IKK-&bgr;, NF-&kgr;B, and Ser307p-IRS-1 expressions were significantly higher in the liver of CP rats than in sham-operated rats (P < 0.05). Rosiglitazone treatment significantly improved hepatic insulin sensitivity and inhibited the IKK-&bgr;, NF-&kgr;B, and Ser307p-IRS-1 expressions in the liver (P < 0.05). Counteraction with peroxisome proliferator–activated receptor-&ggr; by GW9662 attenuated the aforementioned effects of rosiglitazone. Conclusions Rosiglitazone attenuates hepatic insulin resistance induced by CP. The inhibition of hepatic IKK-&bgr; and NF-&kgr;B expressions via peroxisome proliferator–activated receptor-&ggr; may be involved in the therapeutic effect of rosiglitazone.
Postmarketing Surveillance: The Viewpoint of a Newcomer to Pharmacoepidemiology

Prescription-event monitoring (PEM) is a system of postmarketing surveillance for new chemical entities that has been developed by Inman. Its principal aim is to generate hypotheses about adverse drug reactions (ADRs) that have not been identified during clinical trials. The operation covers the whole of England (total population approximately 50 million). Cohorts of 10,000–20,000 patients are identified from photocopies of prescriptions that are provided by the Prescription Pricing Authority. Event data are obtained from a standard questionnaire (green form) that is sent to the prescribing doctor at an interval after the date on the original prescription. Serious events are followed up further via the general practitioner (GP), and deaths are routinely investigated using GP medical records and copies of death certificates. Since 1984, 32 drugs have been included in PEM. The data base is used to provide examples of the methods of data analysis and further follow-up of signals. The future of PEM will be discussed in the context of the general development of pharmacoepidemiology in the United Kingdom. It is concluded that this should acquire a broader perspective, and needs to address issues of recruitment, training and dissemination of information, and that a sound academic base is required.
Pancreatic Ductal Perfusion at Organ Procurement Enhances Islet Yield in Human Islet Isolation

Objective Pancreas preservation is a major factor influencing the results of islet cell transplantation. This study evaluated the effects of 2 different solutions for pancreatic ductal perfusion (PDP) at organ procurement. Methods Eighteen human pancreases were assigned to 3 groups: non-PDP (control), PDP with ET-Kyoto solution, and PDP with cold storage/purification stock solution. Pancreatic islets were isolated according to the modified Ricordi method. Results No significant differences in donor characteristics, including cold ischemia time, were observed between the 3 groups. All islet isolations in the PDP groups had more than 400,000 islet equivalence in total islet yield after purification, a significant increase when compared with the control (P = 0.04 and P < 0.01). The islet quality assessments, including an in vivo diabetic nude mice assay and the response of high-mobility group box protein 1 to cytokine stimulation, also showed no significant differences. The proportion of terminal deoxynucleotidyl transferase dUTP nick-end labeling–positive cells showing apoptosis in islets in the PDP groups was significantly lower than in the control group (P < 0.05). Conclusions Both ET-Kyoto solution and cold storage/purification stock solution are suitable for PDP and consistently resulted in isolation success. Further studies with a larger number of pancreas donors should be done to compare the effects of the PDP solutions.