Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Various Genetic Polymorphisms on the Incidence and Outcome of Severe Sepsis

Several genetic polymorphisms have been identified in patients with sepsis and severe sepsis, such as the tumor necrosis factor-α (TNF-α) and TNF-β genes, the interleukin-1 (IL-1) family, the IL-6, the IL-10, the CD-14, the Toll-like receptors, plasminogen activator inhibitor type 1, and the factor V 1691G-A mutations. In this study, the relationship between the TNF-α 308G/A, the IL-6-174 G/C, the PAI-1, the FVL, the EPCR, and the Cathepsin G (Ars 125 Ser) polymorphisms and the development and outcome of sepsis in pediatric patients was studied. TNF-α 308 G/A, PAI-1 4G/4G, and EPCR mutations influence the risk of severe sepsis in children. IL-6 174 G/C, FVL, and Cathepsin G (Ars 125 Ser) did not influence the incidence and mortality of severe sepsis.
Discrete Flow Networks: Bottleneck Analysis and Fluid Approximations

We conduct bottleneck analysis of a deterministic dynamic discrete-flow network. The analysis presupposes only the existence of long-run averages, and is based on a continuous fluid approximation to the network in terms of these averages. The results provide functional strong laws-of-large-numbers for stochastic Jackson queueing networks since they apply to their sample paths with probability one.
Encapsulated Ruffini‐like endings in human lumbar facet joints

The innervation of the human lumbar facet joint capsule was studied by light and electron microscopy. Small numbers of encapsulated corpuscular endings were identified in the dense fibrous layer. Clusters of 2 types of endings were found: small cylindrical corpuscles (type 1) and large fusiform corpuscles (type 2). The corpuscles were classified structurally as Ruffini‐type endings. The 1st type was predominant and characterised by a compartmentalised receptor complex, a thin perineurial capsule and a narrow subcapsular space. The 2nd type was characterised by a thicker perineurial capsule, a ‘spindle‐like’ receptive complex, and an extensive subcapsular space with capillaries and concentrically oriented fibroblast‐like cells. Both types of endings were innervated mainly by thinly myelinated group III (A delta) and unmyelinated group IV (C) nerve fibres that branched and terminated in the receptor complex. Their sensory endings were intimately related to the collagen fibre bundles as multiple enlarged axonal segments (‘beads’) with ultrastructural features which were characteristic of receptive sites: an accumulation of mitochondria and vesicles, and ‘bare’ areas of axolemma lacking a Schwann cell investment but covered by a thin basal lamina. Some beads in the 2nd type of ending contained granular vesicles, 30–60 mm in diameter, resembling sympathetic nerve endings. Small diameter collagen fibrils situated within multilayered basal laminae were found among the multiple receptive sites in the receptive complex in both types of ending. Their possible functional significance in mechanoreception is discussed. Particular attention has been given to their apparent variable orientation to the mechanoreceptive site.
Identification of cytoskeletal, focal adhesion, and cell adhesion proteins in growth cone particles isolated from developing chick brain

Growth cones are intimately involved in determining the direction and extent of neurite elongation during development They are able to monitor their environment and respond to it by undergoing directed motility. We have isolated a fraction enriched in growth cone particles from embryonic chick brain. Assayed by immunoblots, this fraction is enriched in GAP‐43, and contains the cytoskeletal proteins actin, myosin II, neurofilament protein, tubulin, kinesin, and dynamin. All of the major components of focal adhesions are also present: alpha‐actinin, vinculin, talin, and integrin. In addition to integrin, we also identify the cell adhesion molecules A‐CAM, L1, fibronectin, and laminin in these particles. This preparation of isolated growth cone particles may be a useful model system for studying growth cone adhesion and motility.
Prevalence, disease manifestations, and treatment of psoriatic arthritis in Western Norway.

OBJECTIVE To estimate the prevalence of psoriatic arthritis (PsA) in a geographically defined population, and to characterize the clinical manifestations and medical treatment for PsA. METHODS Prevalent cases were identified for the years 1999-2002 at the rheumatology centers for the population of 442,000 inhabitants. Clinical data were extracted from patient records. Cases with psoriasis and peripheral arthritis and/or radiographic evidence of spondyloarthritis were considered to have PsA, those with other arthritides were excluded. RESULTS In total, 634 patients with PsA were identified from the adult population, equivalent to a prevalence of 1.95 per 1000 (1.80-2.10). There were no significant sex differences in rates; for both sexes the prevalence was highest in the age group 40 to 59 years. Polyarthritis was the most frequent subclass (68.6%). Oligoarthritis, monoarthritis, and arthritis confined to the spine or sacroiliac joints were seen in 22.9%, 5.8%, and 2.7% of cases, respectively. Mean age was higher (50.6 yrs for all cases), and mean disease duration was longer (10.7 yrs) with increasing number of joints affected. The mean erythrocyte sedimentation rate and C-reactive protein were higher with increasing number of joints affected and disease duration. Intraarticular injection of glucocorticoids had been administered to 40.0% of the patients during the last year. Disease modifying antirheumatic drugs were used by 40.0%, with oral methotrexate being the most frequently used. CONCLUSION The estimated prevalence of PsA was 1.95 per 1000 adult inhabitants, which is higher than previously reported. The demographic data support the presence of a shift from mono- and oligoarthritis to polyarthritis and increased inflammatory activity with increasing disease duration. Methotrexate and intraarticular glucocorticoids were frequently used treatments.
Effect of combination therapy with zidovudine and didanosine on neuropsychological functioning in patients with symptomatic HIV disease: a comparison of simultaneous and alternating regimens

Objective:To evaluate the effects of treatment with alternating and simultaneous regimens of zidovudine and didanosine on neuropsychological function in patients with symptomatic HIV-1 disease, focusing on patients with possible HIV-1-associated central nervous system (CNS) compromise at entry. Design:Randomized non-blinded clinical trial. Setting:Government medical research center. Patients:Thirty-eight patients with symptomatic HIV-1 disease, of whom 21 had evidence of CNS compromise at entry. Results:After 12 weeks of therapy, overall significant improvements in memory (P < 0.01) and focused attention (P < 0.001) were seen on both regimens. These gains, however, were largely limited to those patients with HIV-1-associated CNS compromise at entry (P < 0.05). Improvements were also noted in receptive vocabulary, reading, perceptual discrimination and reasoning, divided attention, motor strength, and in mood and affect. Improvements in those latter functions were generally of limited magnitude and were of comparable size for both compromised and non-compromised patients. There was no overall difference between the two drug regimens in the effects on CNS parameters. Conclusions:Therapy-related improvements were noted particularly for patients with HIV-1-associated CNS compromise. Neuropsychological functions that have been implicated in AIDS dementia — memory and attention — showed the greatest gains. In contrast to the previously described superiority of the simultaneous regimen with regard to immunologic and virologic parameters, there was no difference between the regimens with regard to CNS measures. This supports the contention that the CNS constitutes a relatively independent compartment in terms of HIV disease and treatment.
Evolution of Treatment for Diabetic Nephropathy: Historical Progression from RAAS Inhibition and Onward

Abstract The past 2 decades have brought rapid advances in treatment options for chronic kidney disease; however, even with the best treatment, the decline of renal function and progression to end-stage renal disease (ESRD) continues in a significant number of patients. The prognosis of patients with diabetes and ESRD is grim, with < 50% of patients surviving beyond 5 years after diagnosis. Therefore, early recognition and optimal use of available interventions are essential, and research into newer therapeutic targets is needed. This article will review recent advances in our understanding of renal pathophysiology, summarize the evidence to date supporting current treatment options for diabetic nephropathy, and highlight new options that lie on the horizon for the treatment of diabetic kidney disease.
One week of ciprofloxacin before percutaneous nephrolithotomy significantly reduces upper tract infection and urosepsis: a prospective controlled study

Urosepsis after percutaneous nephrolithotomy (PCNL) is a severe complication, and its avoidance can sometimes be difficult despite antibiotic prophylaxis. Authors from the UK with a considerable experience in this procedure describe a prospective controlled study using ciprofloxacin for 1 week before PCNL, and found that it significantly reduces the risk of urosepsis.
Tolerability aspects in duloxetine-treated patients with depression: should one use a lower starting dose in clinical practice?

Objective: This study questions whether a lower starting dose of duloxetine (DLX) could be beneficial for patients with depression, in terms of tolerability and safety in routine clinical care. Research design and methods: Post-hoc analyses of a multicenter, prospective, non-interventional, 6-month study in adult outpatients with a depressive episode was undertaken. Main outcome measures: Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), discontinuations due to TEAEs and hospitalizations due to depression, were all documented at 2 weeks, 4 weeks, 3 months and 6 months after treatment initiation/switch to DLX. Results: Of 4517 patients enrolled, 4313 were included for TEAE evaluation. TEAEs occurred in 17.2% of patients, and SAEs occurred in 0.79% of patients, including one case of suicidal ideation. 1404 patients discontinued within 6 months (TEAEs: n = 119). Starting treatment with 30 mg/day DLX (72.7%) was favored in females, or after inadequate efficacy of previous antidepressant treatment; 60 mg/day DLX was favored in more severe depression and patients receiving concomitant pain medication. Conclusion: Initiating treatment with 60 mg/day DLX was not associated with poorer tolerability in this study. Physicians may be guided by their clinical experience to carefully consider the individual benefit/risk ratio and TEAE susceptibility when deciding to start treatment with a higher or a lower dose of DLX.
Effect of Different Types of Medicaid Managed Care on Childhood Immunization Rates

Medicaid managed care can improve access to prevention services, such as immunization, for low-income children. The authors studied immunization rates for 7,356 children on Medicaid in three managed care programs: primary care case management (PCCM; n = 4,605), a voluntary HMO program (n = 851), and a mandatory HMO program (n = 1,900). Immunization rates (3:3:1 series) in PCCM (78%) exceeded rates in the voluntary HMO program (71%), which in turn exceeded those in the mandatory HMO program (67%). Adjusting for race, urban residence, and gender, compared to children in PCCM, children in the voluntary HMO program were less likely to complete the 3:3:1 series (OR = 0.75, CI = 0.63, 0.90), and children in the mandatory HMO program were even less likely to complete the series (OR = 0.59, CI = 0.51, 0.68). Results differed by individual HMOs. Monitoring of outcomes for all types of managed care by Medicaid agencies is imperative to assure better disease prevention for low-income children.
The t(15;17) translocation alters a nuclear body in a retinoic acid‐reversible fashion.

Nuclear bodies (NBs) are ultrastructurally defined granules predominantly found in dividing cells. Here we show that PML, a protein involved in the t(15;17) translocation of acute promyelocytic leukaemia (APL), is specifically bound to a NB. PML and several NB‐associated proteins, found as auto‐antigens in primary biliary cirrhosis (PBC), are co‐localized and co‐regulated. The APL‐derived PML‐RAR alpha fusion protein is shown to be predominantly localized in the cytoplasm, whereas a fraction is nuclear and delocalizes the NB antigens to multiple smaller nuclear clusters devoid of ultrastructural organization. RA administration (which in APL patients induces blast differentiation and consequently complete remissions) causes the re‐aggregation of PML and PBC auto‐antigens onto the NB, while PML‐RAR alpha remains mainly cytoplasmic. Thus, PML‐RAR alpha expression leads to a RA‐reversible alteration of a nuclear domain. These results shed a new light on the pathogenesis of APL and provide a molecular link between NBs and oncogenesis.
Effects of an Efflux Mechanism and Ribosomal Mutations on Macrolide Susceptibility of Haemophilus influenzae Clinical Isolates

ABSTRACT This study investigated macrolide resistance mechanisms in clinical Haemophilus influenzae strains with different levels of susceptibility to macrolides. A total of 6,382 isolates were collected during the Alexander Project from 1997 to 2000. For 96.9% of these isolates, the azithromycin MICs were 0.25 to 4 μg/ml, and these were defined as baseline strains. For 1.8% of the isolates, the azithromycin MICs were lower (<0.25 μg/ml), and for 1.3% of the isolates, the MICs were higher (>4 μg/ml). These isolates were defined as hypersusceptible and high-level macrolide-resistant strains, respectively. To identify the mechanisms associated with these three susceptibility patterns, representative strains were studied for the presence of macrolide efflux pumps and for ribosomal alterations. Macrolide efflux was studied by measuring the accumulation of radioactive azithromycin and clarithromycin in the presence or absence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), a protonophore. Treatment with CCCP increased the accumulation of macrolides in baseline as well as high-level resistant strains, demonstrating the presence of an efflux mechanism, but not in the 20 hypersusceptible strains tested. Among the 31 strains studied that showed high-level resistance to both azithromycin and clarithromycin, 28 had ribosomal alterations, 7 had mutations in ribosomal protein L4, 11 had mutations in L22, 2 had mutations in 23S rRNA, 8 had multiple mutations, and 3 had no mutations. From these results, we conclude that the vast majority (>98%) of H. influenzae strains have a macrolide efflux mechanism, with a few of these being hyperresistant (1.3%) due to one or several ribosomal mutations. Occasional hypersusceptible strains (1.8%) were found and had no macrolide resistance mechanisms and appeared to be the only truly macrolide-susceptible variants of H. influenzae.
Diffuse Myocardial Fibrosis and Congestive Heart Failure in an Adult Male Chimpanzee

Ependymoblastoma in animals has not been previously reported in the literature. An ependymoma in the spinal cord of a 5Y~month-old dog which shares many features with the neoplasm reported here-especially the formation of ependymal rosettes in a dense population of small round cells containing numerous mitotic figures-has been described. ' That report may be an example of ependymoblastoma in the dog. '
Decision on influenza vaccination among the elderly. A questionnaire study based on the Health Belief Model and the Multidimensional Locus of Control Theory.

OBJECTIVE To create an empirical model, describing factors of importance to the elderly in accepting influenza vaccinations. DESIGN Epidemiologic study with two coupled questionnaires. In September 1996 a 46-item questionnaire was sent to 2147 elderly people (> or = 65 years). The questionnaire comprised questions about general health, and questions based on the Health Belief Model and the Multidimensional Locus of Control Theory. In February 1997 a postcard questionnaire was sent to the same elderly people asking whether they had been vaccinated against influenza in the past season. SETTING All Danish counties. SUBJECTS 2147 persons randomly sampled from the The Civil Registration System. MAIN OUTCOME MEASURE Factors influencing the rate of influenza vaccine uptake in the elderly. Influenza vaccination rates. RESULTS In the high-risk group 51% (95% confidence interval: 46-55%) were vaccinated compared to 29% (26-32%) in the low-risk group as regards influenza. By logistic regression the Health Belief Model dimensions "perceived barriers", "perceived benefits" and "perceived severity" were found to be significant predictors of acceptance of influenza vaccinations. CONCLUSIONS An empirical model based on the Health Belief Model predicting acceptance of influenza vaccinations with a positive predictive value of 91% (87-94%) and a negative predictive value of 86% (83-88%) was obtained.
Additive Effect of Combined Application of Magnesium and MK-801 on Analgesic Action of Morphine

As previously reported, magnesium ions (Mg2+) administered in relatively low doses markedly potentiated opioid analgesia in neuropathic pain, in which the effectiveness of opioids is limited. Considering that Mg2+ behaves like an N-methyl-D-aspartate receptor antagonist, the effect of this ion on the analgesic action of morphine was compared with that of MK-801. Acute pain was evoked by mechanical or thermal stimuli, whereas neuropathic hyperalgesia was induced by streptozotocin (STZ) administration. Magnesium sulphate (40 mg/kg i.p.) or MK-801 (0.05 mg/kg s.c.) administered alone did not modify the nociceptive threshold to acute stimuli or the streptozotocin hyperalgesia but significantly augmented the analgesic action of morphine (5 mg/kg i.p.). Furthermore, if these drugs (i.e. magnesium sulphate and MK-801) were applied concomitantly, a clear additive effect on the analgesic action of morphine occurred in both models of pain. Possible explanations of these observations are discussed.
THE EMERGENCE OF THE UNMARKED IN SECOND LANGUAGE PHONOLOGY

This paper discusses the simplification of forms ending in obstruents by native speakers of Mandarin, in particular two effects that are not obviously motivated by either the native- or the target-language grammars: a tendency to devoice final voiced obstruents and a tendency to maximize the number of bisyllabic forms in the output. These patterns are accounted for within Optimality Theory, which describes a grammar as a set of universal, ranked constraints. It is argued that the devoicing and bisyllabicity effects result from universal markedness constraints that are present in all grammars but that are masked in the learner's native-language grammar by the effects of higher ranking constraints.
Immunization of owl monkeys to Plasmodium falciparum with merozoites from cultures of a knobless clone

Summary Aotus trivirgatus monkeys of karyotype 2 were treated as follows. Three received two injections of purified merozoites of a knobless (K‐) clone of Plasmodium falciparum with muramyl dipeptide as adjuvant; three received similar injections but with merozoites of a wild‐type knobby (K+) strain; three controls received MDP with human erythrocytes in the amounts estimated to be present as contaminants in the merozoite preparations. A month after the second injection all nine monkeys were inoculated with parasites of the wild‐type knobby strain from another infected Aotus. The monkeys that had received the K‐ material developed only extremely low infections markedly different from the infections in the controls. Of those that received K+ material, one died early with low parasitaemia, one was protected and one had the same level of infection as the controls. In the combined group of immunized animals, four out of six were protected.
Anti‐prolactin (PRL) autoantibodies suppress PRL bioactivity in patients with macroprolactinaemia

Objective Macroprolactinaemia, mainly caused by anti‐prolactin (PRL) autoantibodies, is frequently found in patients with hyperprolactinaemia. Characteristically, these patients lack clinical symptoms of hyperprolactinaemia, but the serum bioactive PRL concentrations in vitro measured by the Nb2 bioassay are usually high. In this study, we investigated the causes of the discrepancy and the true biological features of macroprolactin.
Candida albicans-Staphylococcus aureus Polymicrobial Peritonitis Modulates Host Innate Immunity

ABSTRACT Despite advances in medical device fabrication and antimicrobial treatment therapies, fungal-bacterial polymicrobial peritonitis remains a serious complication for surgery patients, those on peritoneal dialysis, and the critically ill. Using a murine model of peritonitis, we have demonstrated that monomicrobial infection with Candida albicans or Staphylococcus aureus is nonlethal. However, coinfection with these same doses leads to a 40% mortality rate and increased microbial burden in the spleen and kidney by day 1 postinfection. Using a multiplex enzyme-linked immunosorbent assay, we have also identified a unique subset of innate proinflammatory cytokines (interleukin-6, granulocyte colony-stimulating factor, keratinocyte chemoattractant, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1α) that are significantly increased during polymicrobial versus monomicrobial peritonitis, leading to increased inflammatory infiltrate into the peritoneum and target organs. Treatment of coinfected mice with the cyclooxygenase (COX) inhibitor indomethacin reduces the infectious burden, proinflammatory cytokine production, and inflammatory infiltrate while simultaneously preventing any mortality. Further experiments demonstrated that the immunomodulatory eicosanoid prostaglandin E2 (PGE2) is synergistically increased during coinfection compared to monomicrobial infection; indomethacin treatment also decreased elevated PGE2 levels. Furthermore, addition of exogenous PGE2 into the peritoneal cavity during infection overrode the protection provided by indomethacin and restored the increased mortality and microbial burden. Importantly, these studies highlight the ability of fungal-bacterial coinfection to modulate innate inflammatory events with devastating consequences to the host.
Identification of the Anthropometric Index that Best Correlates with Fasting Blood Glucose and BMI in Post-Pubescent Female Nigerians

The association between anthropometric indices and the incidence of metabolic disturbances varies between age groups and races. In this study, we report the relationship between fasting blood glucose (FBG) and some anthropometric markers of body mass and central obesity in a population of postpubescent female Nigerians (16-23 years). After obtaining written consent from each of the 178 subjects; and the completion of a questionnaire on individual demographics, we collected the following anthropometric data: waist circumference (WC), hip circumference (HC), height (H), and weight (W). We also estimated the body mass index (BMI), waist to hip ratio (WHR), and waist to height ratio (WHtR). Fasting blood glucose (FBG) was estimated using a glucometer. The mean FBG was 83.65 mg/dl and this was best positively and significantly correlated with BMI (r=0.15; P<0.05) in this population. Besides, among other obesity markers, WHtR was most strongly and significantly correlated with BMI (r=0.70; P<0.05). Our data shows that in young (post-pubescent) female Nigerians, the best anthropometric indicator of FBG (and thus of metabolic status), is the BMI, and this is most strongly correlated with WHtR in this particular population. Key words: Fasting blood glucose; Anthropometric index; Post-pubescent Nigerians; BMI; WHR; WHtR