Miracle-dz/UniFAR-FTUs huggingface dataset:
Open Fractures of the Tibia Treated by Immediate Intramedullary Tibial Nail Insertion Without Reaming: A Prospective Study

Objective: Does immediate tibial nail insertion without reaming as part of protocol-driven management provide a safe and effective treatment for open tibia fractures? Study Design: Prospective cohort. Setting: Level 1 trauma center. Patients: A consecutive series of 161 patients with Gustilo grade I-IIIb open tibia fractures. Intervention: Emergent incision and debridement of the wound with immediate tibial nail insertion without reaming, repeat incision and debridement, and soft-tissue coverage within 14 days. Main Outcome Measurements: Time to union, number of secondary procedures performed to obtain union, implant failures, and the type and incidence of complications. Results: One hundred and forty-three fractures were followed to union. Follow up averaged 2.2 years (0.6-5.5 years). Seventy-six fractures united in less than 6 months, 35 took between 6 and 9 months, and 32 took longer than 9 months. Twenty-five additional procedures were needed to obtain union in 16 of the delayed unions (12 nail exchanges, 4 bone grafts, 9 dynamizations). Complications included 3 patients with cellulitis, 1 superficial infection, 4 deep infections (1 grade I, 2 grade II, 1 grade IIIb), 3 loose screws, 2 broken screws, 5 malunions greater than 5 degrees, and 30 patients with decreased ankle motion when compared with the uninjured side. Not counting the ankle loss of motion, 18 complications occurred in 143 fractures (13%). Twenty-nine patients (20%) had complaints of minor knee pain and 30 (21%) had occasional fracture site pain after activity despite clinical and radiographic evidence of union. Eleven patients (8%) considered themselves completely disabled. Five patients were not treated by the standard protocol and are not included in the previously listed statistics; 3 were grade IIIB that did not have adequate coverage by 14 days, and 2 were grade II injuries that did not have a second debridement. Four of these 5 patients developed a complication. Conclusions: Protocol-driven management emphasizing meticulous soft-tissue management and the use of immediate tibial nailing without reaming appears to be safe and effective in the treatment of open tibia fractures. The deep infection rate for the patients who were treated by protocol was 3% and the implant failure rate was lower than has been previously reported, most likely attributable to attempts to obtain cortical contact and avoid fracture gaps. Overall satisfaction was good, but approximately 41% of the patients had complaints of knee or fracture site pain or both well after union.
Bivalent role of the phosphatidylinositol‐3‐kinase (PI3K) during influenza virus infection and host cell defence

Infections with influenza A viruses result in the activation of a variety of intracellular signalling pathways. Recent findings suggest that in response to double‐stranded RNA (dsRNA), which is commonly used as a mimic for accumulating viral RNA, the phosphatidylinositol‐3‐kinase (PI3K) is activated and mediates activation of the transcription factor interferon regulatory factor 3 (IRF‐3). Thus, we investigated the function of PI3K during influenza virus infection. The pathway was activated upon infection and consistent with earlier findings using dsRNA, inhibition of PI3K itself or block of signalling by the PI3K product, the second messenger phosphatidylinositol‐3,4,5‐trisphosphate (PIP3), results in misphosphorylation and impaired dimerization of IRF‐3 as well as reduced IRF‐3‐dependent promoter activity. This would imply an antiviral function of the kinase in influenza virus‐infected cells. However, upon inhibition of PI3K, titers of progeny virus were reduced rather than enhanced. This was coincident with a strong decrease of viral protein accumulation that was not due to a block of protein synthesis or inhibition of the viral polymerase complex. Immunofluorescence studies revealed that PI3K rather appears to regulate a very early step during viral entry. Thus PI3K is a perfect example of a seemingly antiviral signalling component that is misused by the virus to support effective replication.
The Pattern of Surgical Cancers in Nigeria: The Benin Experience

Nylander" in a detailed study of the frequency of twinning in the district found that the twinning rate was 45/1000 live births, 92.6% being of the dizygotic type. It is expected that multiple ovulation will be a predisposing factor to the occurrence of ectopic pregnancy. However, the low incidence of ectopic pregnancy, the small number associated with intrauterine pregnancy and the absence of bilateral ectopic pregnancy in this series (compared with 0.4% in the Accra study) show that high twinning rate alone without other predisposing factors especially PID may not cause increased incidence of ectopic pregnancy. Autotransfusion has been a major feature in the management of patients in this series having been employed in 107 patients (91%). This was necessitated by the difficult condition of the practice: poor transportation, absence of national electric power supply, and therefore no facility for blood banking, and the reluctance of the populace to donate blood. This contrasts with the experience at Korle Bu Teaching Hospital, Accra, Ghana, where in a series of 1255 ectopic pregnancies, autotransfusion was not performed and 663 units of homologous blood were transfused 1.
O6-benzylguanine potentiates the in vivo toxicity and clastogenicity of temozolomide and BCNU in mouse bone marrow.

The effects of treatment of mice with O6-benzylguanine (O6-BeG) on the levels of O6-alkylguanine-DNA alkyltransferase (ATase) in the hematopoietic compartment and on the in vivo sensitivity of hematopoietic progenitor cells to the toxic and clastogenic effects of the antitumor agents 1,3-bis(2-chloroethyl)-nitrosourea (BCNU) and temozolomide were studied. When the overall effects of BCNU alone or with O6-BeG pretreatment were compared, dose potentiating factors of 4.17 for marrow cellularity, 4.57 for granulocyte macrophage-colony forming cells (GM-CFC) and 8.25 for colony forming unit-spleen (CFU-S) in O6-BeG pretreated versus nonpretreated animals were observed. A similar trend of dose potentiation was observed for temozolomide, although it was of lower magnitude: 1.20 for marrow cellularity, 1.63 for GM-CFC, and 1.68 for CFU-S. When the clastogenic effects of BCNU and temozolomide were examined in the mouse bone marrow micronucleus assay, a significantly (P < .05 to .001) higher frequency of micronuclei formation was observed in mice that received O6-BeG pretreatment compared with mice that received no pretreatment. These data suggest that the use of O6-BeG as a tumor-sensitizing agent before treatment of patients with O6-alkylating agents may lead to more severe hematological toxicity and possibly to an increased incidence of secondary leukemias as a result of elevated mutation frequencies in these patients.
CarD uses a minor groove wedge mechanism to stabilize the RNA polymerase open promoter complex

A key point to regulate gene expression is at transcription initiation, and activators play a major role. CarD, an essential activator in Mycobacterium tuberculosis, is found in many bacteria, including Thermus species, but absent in Escherichia coli. To delineate the molecular mechanism of CarD, we determined crystal structures of Thermus transcription initiation complexes containing CarD. The structures show CarD interacts with the unique DNA topology presented by the upstream double-stranded/single-stranded DNA junction of the transcription bubble. We confirm that our structures correspond to functional activation complexes, and extend our understanding of the role of a conserved CarD Trp residue that serves as a minor groove wedge, preventing collapse of the transcription bubble to stabilize the transcription initiation complex. Unlike E. coli RNAP, many bacterial RNAPs form unstable promoter complexes, explaining the need for CarD. DOI: http://dx.doi. org/10.7554/eLife.08505. 001
Intravitreal Injections of Bevacizumab Plus Methotrexate versus Bevacizumab Alone for the Treatment of Diabetic Macular Edema: A Randomized, Sham-Controlled Trial

Purpose: To evaluate the efficacy of intravitreal bevacizumab (IVB) combined with intravitreal methotrexate (IVM) in the treatment of diabetic macular edema (DME). Methods: In this prospective, interventional contralateral eye study, patients with bilateral DME were randomly allocated to receive three monthly injections of IVB (1.25 mg/0.05 mL) plus IVM (400 μg; 0.16 cc) or IVB alone. The outcome measure was changes in the best corrected visual acuity (BCVA), central macular thickness (CMT), and central macular volume (CMV). Results: Thirty-six treatment-naive eyes of 18 patients with a mean age of 62.38 ± 6.2 years were included in the study. BCVA logMAR changed from 0.95 ± 0.53 at baseline to 0.75 ± 0.53 in the combination group and from 0.72 ± 0.57 to 0.49 ± 0.50 in the IVB alone group at 1 month after the 3rd injection. BCVA improvement in both groups was not statistically significant compared with the baseline value (P > 0.99). Compared with the baseline values, mean CMT and CMV were reduced in both groups; however, these changes did not reach a significant level. The differences of CMT changes between the groups were not statistically significant at month 1 (P = 0.82), month 2 (P = 0.21), and month 3 (P = 0.10). Furthermore, the differences of CMV changes between the groups were not statistically significant at month 1 (P = 0.76), month 2 (P = 0.82), and month 3 (P = 0.11). Conclusions: This pilot study demonstrated no significant therapeutic effects for IVB combined with IVM compared to IVB alone in treatment-naive DME patients over a 3-month course.
Investigating the presence of fungal agents in febrile neutropenic patients with hematological malignancies using different microbiological , serological , and molecular methods

This study aimed to investigate fungal agents in febrile neutropenic patients with hematological malignancies. Direct microscopy and cultures were performed on clinical samples collected from febrile neutropenic episodes. The galactomannan (GM) antigen was tested using enzymelinked immunosorbent assays, and Aspergillus fumigatus and Candida albicans deoxyribonucleic acid (DNA) assessed using real-time polymerase chain reaction (PCR) in consecutive serum samples. Of the 199 episodes investigated, 1.5% were classified as definite invasive aspergillosis (IA), 4.0% as IA with high probability, and 4.0% as IA with low probability. Additionally, candidaemia was detected in eight episodes (4.1%). The GM antigen was found negative for 86.4% of episodes, as one positive for 7.0% of episodes, as two or more consecutive positives for 5.5% of episodes, and as positive in any two serum samples in 1.0% of episodes. While no C. albicans DNA was detected in 98.5% of 199 episodes, one positive result was obtained in 1.0% of episodes, and two or more consecutive positives in 0.5% of episodes. A. fumigatus PCR results were found negative in 81.9% of episodes, as one positive in 16.1% of episodes, as positive in any two serum samples in 1.0% of episodes, and consecutively positive in 1.0% of episodes. GM antigen tests were found consecutively positive in all three patients diagnosed as having definite IA. These findings indicate that conventional, serological, and molecular methods should be used in combination to detect fungal agents in febrile neutropenic patients.
Entropic principle and asymptotic freedom

Motivated by the recent developments about the Hartle-Hawking wave function associated to black holes, we formulate an entropy functional on the moduli space of Calabi-Yau compactifications. We find that the maximization of the entropy is correlated with the appearance of asymptotic freedom in the effective field theory. The points where the entropy is maximized correspond to points on the moduli which are maximal intersection points of walls of marginal stability for Bogomolnyi-Prasad-Sommerfield states. We also find an intriguing link between extremizing the entropy functional and the points on the moduli space of Calabi-Yau three folds which admit a "quantum deformed" complex multiplication.
Glucose as a prognostic factor in ovarian carcinoma

Research suggests that glucose levels in cancer patients may be an important prognostic indicator. In ovarian tumors, increased expression of glucose transporter 1 (GLUT1), a transmembrane protein responsible for glucose uptake, is related to shorter survival time in ovarian cancer patients. This study tested the hypothesis that higher presurgical glucose levels predict shorter disease‐specific survival time and time to recurrence in ovarian cancer patients.
Multiplicative interaction between intrathecally and intracerebroventricularly administered mu opioid agonists but limited interactions between delta and kappa agonists for antinociception in mice.

Simultaneous action of morphine on supraspinal and spinal sites produces a multiplicative interaction for antinociception which may be important for the analgesia produced by systemically administered morphine. The purpose of this study was to see whether other agonists with more receptor selective opioid actions than morphine would also produce this multiplicative interaction. DAMPGO (Tyr-D-Ala2-Gly-NMePhe4-Gly-ol5), DPDPE (D-Pen2, D-Pen5, enkephalin) and U50-488H, opioid agonists highly selective for mu, delta and kappa receptors, respectively, were administered alone i.c. v. or intrathecally (i.t.) or in combination (i.c.v. plus i.t.) to determine ED50 values for the tail-flick response in mice. These ED50 values were examined isobolographically in relation to the theoretical additive ED50 values by the potency ratio method. First, DAMPGO given i.cv and i.t. was similar to morphine, indicating that simultaneous supraspinal and spinal mu agonist administration produce the multiplicative interaction. Second, concurrent administration of DPDPE or U50,488H, i.c. v. and i.t. , as well as cross-over combinations of DPDPE at one and U50,488H at the other site, produced additive interactions only. The multiplicative interaction was a property characteristic of mu but not delta and kappa agonists. Based on the similarity between morphine and DAMPGO, it was postulated that both mu agonists act on redundant descending pain inhibitory pathways to produce multiplication. A second mechanism for multiplicative interaction was based on the difference between DAMPGO and morphine. (ABSTRACT TRUNCATED AT 250 WORDS)
The relationship between antibiotic residue violations and somatic cell counts in Wisconsin dairy herds.

The objective of this retrospective observational study was to characterize somatic cell counts (SCC) on Wisconsin dairy farms and to determine the relationship between SCC and the risk of antibiotic residue violation. Monthly official state regulatory data were used when both the bulk tank SCC value and antibiotic test results were available for the same date. Data were collected from Wisconsin dairy farms from January 1995 through November 1998 and consisted of results of tests performed on 805,772 grade A and 176,763 grade B milk samples. Herd-year SCC averages were used to classify herds (< or =250,000; 251,000 to 400,000, 401,000 to 550,000, 551,000 to 700,000, >700,000), and the relative risk of antibiotic residue by SCC class was determined. Arithmetic mean SCC values were 334,634 and 480,029 for grade A and grade B milk, respectively. SCC values were significantly higher for samples with positive antibiotic residue tests for grade A milk during all 4 yr tested. The SCC values were significantly higher for samples with positive antibiotic residue tests for grade B milk for 3 of 4 yr. The rate of antibiotic residue violation per 1000 herd-years increased with SCC class for both grade A and grade B milk. The relative risks of antibiotic residue violation by SCC class were 1.0, 1.43, 2.38, 2.78, and 7.10 for grade A milk and 1.0, 1.11, 2.67, 4.33, and 5.43 for grade B milk. Programs to reduce the level of subclinical mastitis on dairy farms may have an additional benefit of reducing the risk of antibiotic residue violations.
Meningiomas With Rhabdoid Features Lacking Other Histologic Features of Malignancy: A Study of 44 Cases and Review of the Literature

The behavior of rhabdoid meningiomas otherwise lacking malignant features remains unknown as most of the originally reported aggressive cases showed anaplastic histologic features independently of rhabdoid phenotype. We studied 44 patients with rhabdoid meningiomas lacking anaplastic features. Median age at diagnosis was 48.6 years (range 10–79). Location was supratentorial in 28 (63.6%), skull base in 15 (34.1%), and spinal in 1 (2.3%). Tumor grade was otherwise World Health Organization grade I (n = 22, 50%) or II (n = 22, 50%). Rhabdoid cells represented <20% of the tumor in 12 cases (27.3%), 20% to 50% in 18 (40.9%), and >50% in 14 (31.8%). Median clinical follow-up, available for 38 patients, was 5.0 years (range 0.17–14.2). Recurrence occurred in 9 patients (5-year recurrence-free survival, 73.7%) with a significantly higher risk in subtotally resected tumors (p = 0.043). Rhabdoid cell percentage was not associated with recurrence. Six patients died (4 of disease, 2 of unclear causes); 5-year overall survival was 86.7%, a mortality in excess of that expected in grade I–II meningiomas but much lower than originally reported. Review of 50 similar previously reported cases confirmed our findings. We suggest that rhabdoid meningiomas be graded analogously to nonrhabdoid tumors, with caution that some may still behave aggressively and close follow-up is recommended.
Is Alzheimer's disease a synaptic disorder?

BACKGROUND In Alzheimer's disease (AD), the common symptom is loss of memory. Learning and memory are associated with amoeboid movements of synaptic endings. Docosahexaenoic acid (DHA) is a major lipid constituent of synaptic end sites. Minor changes in the fluidity of phospholipidic membranes have a dramatic impact on the function of synapses, where membrane fluidity may influence the neurotransmitter receptor activity. METHOD Studies pertaining to the role of DHA as a neuroprotective agent was reviewed. RESULTS Here we will show a conceptual framework for the role of DHA in the prevention of AD. The DHA content has been shown to be decreased in the brain and plasma of patients affected by AD. Aspirin triggers the generation of DHA-derived mediators that are themselves neuroprotective. CONCLUSION Adequate dietary intakes of the neuroprotective DHA (and aspirin? ) may slow down the progression of AD. An essential reserve of synapses from early development is needed.
Lack of Peripheral Memory B Cell Responses in Recovered Patients with Severe Acute Respiratory Syndrome: A Six-Year Follow-Up Study

Six years have passed since the outbreak of severe acute respiratory syndrome (SARS). Previous studies indicated that specific Abs to SARS-related coronavirus (SARS-CoV) waned over time in recovered SARS patients. It is critical to find out whether a potential anamnestic response, as seen with other viral infections, exists to protect a person from reinfection in case of another SARS outbreak. Recovered SARS patients were followed up to 6 y to estimate the longevity of specific Ab. The specific memory B cell and T cell responses to SARS-CoV Ags were measured by means of ELISPOT assay. Factors in relation to humoral and cellular immunity were investigated. Six years postinfection, specific IgG Ab to SARS-CoV became undetectable in 21 of the 23 former patients. No SARS-CoV Ag-specific memory B cell response was detected in either 23 former SARS patients or 22 close contacts of SARS patients. Memory T cell responses to a pool of SARS-CoV S peptides were identified in 14 of 23 (60.9%) recovered SARS patients, whereas there was no such specific response in either close contacts or healthy controls. Patients with more severe clinical manifestations seemed to present a higher level of Ag-specific memory T cell response. SARS-specific IgG Ab may eventually vanish and peripheral memory B cell responses are undetectable in recovered SARS patients. In contrast, specific T cell anamnestic responses can be maintained for at least 6 y. These findings have applications in preparation for the possible reemergence of SARS.
Epitope variability of Bcl-2 immunolocalization in the human corneal epithelium.

PURPOSE To further study the immunological localization of Bcl-2 protein in human corneal epithelium. METHODS Three anti-human Bcl-2 antibodies, generated against amino acid residues (aa) 4-21 (polyclonal), 1-205 (monoclonal), and 41-54 (monoclonal), were used to localize Bcl-2 protein immunocytochemically in fresh eye bank donor human corneas. RESULTS In the central corneal epithelium, two anti-Bcl-2 antibodies (aa 4-21 and aa 1-205) showed intense cytoplasmic staining of basal epithelial cells. These antibodies produced similar staining in the limbal epithelium, with gradually less intense staining of wing and superficial cells. By contrast, as previously reported, a monoclonal antibody to aa 41-54 stained nuclei of all epithelial cell layers with the exception of some surface corneal epithelial cells; this antibody also demonstrated very bright anti-Bcl-2 staining of Langerhans cells localized in the peripheral corneal epithelium. CONCLUSION In our previous study, Bcl-2 protein was immunocytochemically localized to the nuclear compartment of all corneal epithelial cell layers with the use of antibodies specific for the regulatory flexible loop domain of Bcl-2. However, Bcl-2 can also be uniquely localized to the cytoplasm of the corneal epithelium with the use of antibodies generated against aa 4-21 and aa 1-205. Taken together, these results using epitope specific antibodies indicate that different epitopes on the Bcl-2 protein are available for antibody binding within different cells and cellular compartments, suggesting that proliferation and differentiation may lead to changes in the Bcl-2 structure and conformation within different compartments of the epithelial cells themselves.
Human RNase L tunes gene expression by selectively destabilizing the microRNA-regulated transcriptome

Significance The mammalian innate immune system recognizes double-stranded RNA (dsRNA) as a signature of infections and cell damage. Cells exposed to dsRNA release interferons to activate protective programs in surrounding tissues. One of these protective programs triggers regulated decay of intracellular RNA by the pseudokinase/endoribonuclease RNase L. Here we map the pathway of this RNA decay transcriptome-wide and identify groups of selectively destabilized human messenger RNAs. We show that RNA decay by RNase L has an important role in homeostasis and serves as a suppressor of cell adhesion. Our work defines the targets of RNase L and clarifies the role of the dsRNA-activated messenger RNA decay in the interferon response. Double-stranded RNA (dsRNA) activates the innate immune system of mammalian cells and triggers intracellular RNA decay by the pseudokinase and endoribonuclease RNase L. RNase L protects from pathogens and regulates cell growth and differentiation by destabilizing largely unknown mammalian RNA targets. We developed an approach for transcriptome-wide profiling of RNase L activity in human cells and identified hundreds of direct RNA targets and nontargets. We show that this RNase L-dependent decay selectively affects transcripts regulated by microRNA (miR)-17/miR-29/miR-200 and other miRs that function as suppressors of mammalian cell adhesion and proliferation. RNase L mimics the effects of these miRs and acts as a suppressor of proliferation and adhesion in mammalian cells. Our data suggest that RNase L-dependent decay serves to establish an antiproliferative state via destabilization of the miR-regulated transcriptome.