Miracle-dz/UniFAR-FTUs huggingface dataset:
Drug Resistance in Mycobacterium tuberculosis

Tuberculosis (TB) remains to be a serious health problem worldwide. There is an increased transmission of Mycobacterium tuberculosis strains with drug resistance, hence complicat‐ ing TB control. The deciphering of the M. tuberculosis genome, together with the imple‐ mentation of new molecular biology tools, has allowed the identification of changes in nucleic acid sequences with a functional impact. These mutations have become important in the design of early‐diagnostic kits to identify the resistance profile of M. tuberculosis . Since the conventional methods to determine the identity of M. tuberculosis strains based in cultures are laborious, time‐consuming and performed by specialized technicians, the result is generated until 4 months after receiving the samples. During this time, patients with TB are not adequately treated, and resistant strains may be transmitted to the rest of the population. In this chapter, we describe the most relevant mutations in genes associ‐ ated with drug resistance in M. tuberculosis , the analysis of gene expression to identify new markers of drug resistance strains, and the development of new antituberculosis drugs against drug‐resistant strains.
Are risk factors for patellofemoral and tibiofemoral knee osteoarthritis different?

OBJECTIVE To determine whether patellofemoral (PF), tibiofemoral (TF), and combined patterns of knee osteoarthritis (OA) differ in their strengths of associations with any of the known risk factors for knee OA, and especially to evaluate whether body mass index (BMI) correlates with all 3 patterns, or only with tibiofemoral disease, as previously suggested. METHODS We obtained anteroposterior and lateral knee radiographs on 608 participants at the 22nd biennial examination of the Framingham cohort study (1992-3). The presence or absence of OA in the TF and PF compartments of each knee was scored, and subjects were classified on the basis of the pattern of compartmental involvement in their 2 knees. The strength of association of age, sex, BMI, chondrocalcinosis, and knee injury was computed for PF, TF, and combined pattern of knee OA using multiple logistic regression. RESULTS The mean age and BMI of the sample were 80.7 yrs (SD 5.0) and 25.4. kg-2 (SD 3.7), respectively. PF, TF, and combined patterns of knee OA were present in 5.3, 23.0 and 19.7%, respectively. Elevated BMI was a risk factor for all 3 patterns of disease (adjusted OR for highest vs lowest tertile of BMI 3.7, 1.9, and 7.0 for PF, TF, and combined pattern, respectively). Risk factor profiles were broadly similar for TF and PF OA, with the possible exception of knee injury in men (adjusted OR = 2.0 for PF, 3.7 for TF OA). Risk factors were generally more strongly associated with the combined pattern of OA. CONCLUSION Obesity is an important risk factor for PF, TF, and combined patterns of knee OA. The relationships of these patterns with the risk factors investigated here appear similar and are strongest for the combined pattern.
Clinically recurrent primary sclerosing cholangitis following liver transplantation: A time course

Orthotopic liver transplantation (OLT) is the treatment of choice for patients with end‐stage primary sclerosing cholangitis (PSC). This study sought to chronicle the natural history of PSC recurrence following OLT and identify clinical variables that may contribute to disease reemergence. From 1988 to 2006, 1102 OLTs were performed in 1032 adults at the University of Colorado Health Sciences Center. Of these, 130 patients (12.6%) with PSC received 146 allografts. Recurrence was defined by a clinically worsening examination and radiographic evidence. A total of 9 potential predictors were considered, using both bivariate log rank and multivariate Cox analysis, including: age > 55, gender, surgical technique (piggyback technique), presence of inflammatory bowel disease, intact colon before transplant, or cholangiocarcinoma (CCA), cold ischemia time, sirolimus‐based immunosuppression, and graft type. The 1, 5, and 10‐year recurrence‐free survival was 91%, 76%, and 61%, respectively. The crude incidence of disease recurrence was 22 of 130 patients or 16.9%. Patients' risk of recurrent PSC at 1, 5, and 10 years was 2%, 12%, and 20%, respectively (mortality censored). Of the 22 patients that developed recurrent disease, 7 received a second transplant. Of the 9 factors considered, the presence of CCA prior to OLT is significantly predictive of disease recurrence [risk ratio (RR) = 3.77; P = 0.0038]. Once a patient was diagnosed with recurrent disease, the median survival without receiving a second transplant was 39.1 months (95% confidence interval: 27.6‐50.6 months). In conclusion, recurrent PSC following OLT is a formidable but protracted problem following OLT. Patients may require a second transplant following reemergent disease with reasonable survival benefit. Liver Transpl 14:181–185. 2008. © 2008 AASLD.
AF relaying for Multiple Antenna Multiple Relay Networks under individual power constraint at each relay

This paper investigates the optimal beamforming weight matrix for Multiple-Antenna Multiple-Relay (MAMR) Networks. It is assumed that each relay makes use of the Amplify and Forward (AF) strategy, i.e., it multiplies the received signal vector by a matrix, dubbed the relay weight matrix, and forwards the resulting vector to the destination. The relay weight matrices have to be concurrently designed to optimize a desired criterion at the destination, assuming each relay node is subject to a power constraint. In this work, the Mean Square Error (MSE) metric is assumed to be the corresponding cost function. In this regard, it is demonstrated that the aforementioned problem can be cast as a convex optimization problem in which the individual power constraints are tackled by employing the method of Lagrange multipliers. Then, it is demonstrated that the optimal solution can be tackled in two-fold. First, an elegant analytical method for the corresponding dual problem is devised; rendering the current complex vector optimization problem can be translated to a scalar optimization problem. Then, these scalar variables are computed numerically. Numerical results are provided, showing the Bit Error Rate (BER) achieved through using the proposed method outperforms that of MMSE-MMSE method introduced by Oyman et.al., which is regarded as the best known method for such problem.
Functional Analysis of Lactobacillus rhamnosus GG Pili in Relation to Adhesion and Immunomodulatory Interactions with Intestinal Epithelial Cells

ABSTRACT Lactobacillus rhamnosus GG, a probiotic with good survival capacity in the human gut, has well-documented adhesion properties and health effects. Recently, spaCBA-encoded pili that bind to human intestinal mucus were identified on its cell surface. Here, we report on the phenotypic analysis of a spaCBA pilus knockout mutant in comparison with the wild type and other adhesin mutants. The SpaCBA pilus of L. rhamnosus GG showed to be key for efficient adherence to the Caco-2 intestinal epithelial cell (IEC) line and biofilm formation. Moreover, the spaCBA mutant induces an elevated level of interleukin-8 (IL-8) mRNA in Caco-2 cells compared to the wild type, possibly involving an interaction of lipoteichoic acid with Toll-like receptor 2. In contrast, an L. rhamnosus GG mutant without exopolysaccharides but with an increased exposure of pili leads to the reduced expression of IL-8. Using Transwells to partition bacteria from Caco-2 cells, IL-8 induction is blocked completely regardless of whether wild-type or mutant L. rhamnosus GG cells are used. Taken together, our data suggest that L. rhamnosus GG SpaCBA pili, while promoting strong adhesive interactions with IECs, have a functional role in balancing IL-8 mRNA expression induced by surface molecules such as lipoteichoic acid.
Personality traits and psychological distress in persons with chronic tension‐type headache. The Akershus study of chronic headache

Aaseth K, Grande RB, Leiknes KA, Benth JŠ, Lundqvist C, Russell MB. Personality traits and psychological distress in persons with chronic tension‐type headache. The Akershus study of chronic headache. Acta Neurol Scand: 2011: 124: 375–382. © 2011 John Wiley & Sons A/S.
Neural bases of atypical emotional face processing in autism: A meta-analysis of fMRI studies

Abstract Objectives. We aim to outline the neural correlates of atypical emotional face processing in individuals with ASD. Methods. A comprehensive literature search was conducted through electronic databases to identify functional magnetic resonance imaging (fMRI) studies of whole brain analysis with emotional-face processing tasks in individuals with ASD. The Signed Differential Mapping with random effects model was used to conduct meta-analyses. Identified fMRI studies were further divided into sub-groups based on contrast (“emotional-face vs. non-emotional-face” or “emotional-face vs. non-face”) to confirm the results of a meta-analysis of the whole studies. Results. Thirteen studies with 226 individuals with ASD and 251 typically developing people were identified. We found ASD-related hyperactivation in subcortical structures, including bilateral thalamus, bilateral caudate, and right precuneus, and ASD-related hypoactivation in the hypothalamus during emotional-face processing. Sub-analyses with more homogeneous contrasts preserved the findings of the main analysis such as hyperactivation in sub-cortical structure. Jackknife analyses showed that hyperactivation of the left caudate was the most robust finding. Conclusions. Abnormalities in the subcortical structures, such as amygdala, hypothalamus and basal ganglia, are associated with atypical emotional-face processing in individuals with ASD.
Human adenovirus-specific CD8+ T-cell responses are not inhibited by E3-19K in the presence of gamma interferon

Adenovirus has considerable potential as a gene therapy vector, but recent animal data suggest that transduced cells are destroyed by adenovirus-specific cytotoxic T-lymphocyte (CTL) responses. Therefore, it will be important to develop strategies to evade adenovirus-specific CTL responses in humans. As a first step, an assay was developed to detect and characterize human CTLs directed against adenovirus. Adenovirus-specific CTL responses were demonstrated to be present in four of five healthy adults by in vitro stimulation of peripheral blood mononuclear cells with autologous fibroblasts infected with the adenovirus type 2 (Ad2) E3 deletion mutant Ad2+ND1. Killing by adenovirus-specific CTLs was major histocompatibility complex class I restricted and was documented to be mediated by CD8+ T cells. Wild-type-Ad2-infected cells were poor CTL targets compared with cells infected with the E3 deletion mutant because of the expression of E3-19K, an early viral glycoprotein which prevents transport of major histocompatibility complex class I antigens out of the endoplasmic reticulum to the cell surface. However, preincubation of targets with gamma interferon resulted in enhanced killing of wild-type-Ad2-infected cells, to levels comparable to those obtained with Ad2+ ND1-infected cells. Radioimmunoprecipitation analysis revealed that gamma interferon not only increased the synthesis of class I antigens but also allowed excess molecules to escape from the endoplasmic reticulum. It is concluded that E3-19K expression in adenovirus-infected cells inhibits human CTL recognition in vitro but that gamma interferon may help overcome the E3-19K effect during acute infection in vivo.
Photochemically crosslinked matrices of gelatin and fibrinogen promote rapid cell proliferation

Here we report the use of a facile photochemical crosslinking method to fabricate stable polymer matrices from unmodified gelatin and fibrinogen. Gels were produced by covalent crosslinking of the proteins in a rapid photo‐oxidative process, catalysed by a ruthenium metal complex and irradiation with visible light. For generation of macroporous, spongy matrices, the proteins and crosslinking reagents were mixed with catalase and hydrogen peroxide to achieve a foaming reaction, producing a stable, foamed matrix that was subsequently photo‐crosslinked. C2C12 cells were either seeded onto the matrices after photo‐curing or embedded in the protein matrix prior to foaming and crosslinking. Cells seeded onto scaffolds post‐curing showed high cell viability and rapid proliferation in vitro. For cells embedded in the matrix prior to crosslinking there was some loss of initial viability, but surviving cells were able to proliferate after a period of in vitro cultivation. The matrices were shown to be biocompatible when implanted into nude mice, with evidence of proliferation and differentiation of cells seeded into the scaffolds. The results are promising for further development of tissue‐engineering scaffolds based on this ruthenium‐catalysed photo‐crosslinking method. Copyright © 2010 John Wiley & Sons, Ltd.
Comparison of the effects of mepivacaine and lidocaine on rat myocardium

Background and objective: To compare the inotropic and lusitropic effect of lidocaine and mepivacaine on rat papillary muscle. Methods: Effects of lidocaine and mepivacaine (10−8−10−3 M) were studied in rat left ventricular papillary muscles in vitro at a calcium concentration of 1 mmol, under low (isotony) and high (isometric) loads. Results: Lidocaine induced a significant negative inotropic effect in isotonic and isometric conditions whereas mepivacaine did not. Mepivacaine only induced a negative inotropic effect when added as a bolus for the highest concentration and this effect was significantly more pronounced with lidocaine than with mepivacaine (active force at 10−3 M: 63 ± 10 vs. 84 ± 10% of baseline, P < 0.05). Increasing calcium concentration resulted in a greater positive inotropic effect in the control (199 ± 11% of baseline) and mepivacaine groups (197 ± 22% of baseline) when compared to the lidocaine group (163 ± 19% of baseline, P < 0.05 vs. lidocaine and control groups), suggesting an impairment on intracellular Ca2+ handling by lidocaine. A negative lusitropic effect under low load was observed only for mepivacaine and suggested an impairment of sarcoplasmic reticulum function. Lidocaine and mepivacaine did not modify postrest potentiation but significantly depressed the force–frequency relationship. Conclusions: The negative inotropic and lusitropic effects induced by lidocaine were more important than that of mepivacaine and may involve an impairment of intracellular Ca2+ handling.
Switch over from intravenous to oral therapy: A concise overview

Majority of the patients admitted to a hospital with severe infections are initially started with intravenous medications. Short intravenous course of therapy for 2-3 days followed by oral medications for the remainder of the course is found to be beneficial to many patients. This switch over from intravenous to oral therapy is widely practiced in the case of antibiotics in many developed countries. Even though intravenous to oral therapy conversion is inappropriate for a patient who is critically ill or who has inability to absorb oral medications, every hospital will have a certain number of patients who are eligible for switch over from intravenous to oral therapy. Among the various routes of administration of medications, oral administration is considered to be the most acceptable and economical method of administration. The main obstacle limiting intravenous to oral conversion is the belief that oral medications do not achieve the same bioavailability as that of intravenous medications and that the same agent must be used both intravenously and orally. The advent of newer, more potent or broad spectrum oral agents that achieve higher and more consistent serum and tissue concentration has paved the way for the popularity of intravenous to oral medication conversion. In this review, the advantages of intravenous to oral switch over therapy, the various methods of intravenous to oral conversion, bioavailability of various oral medications for the switch over program, the patient selection criteria for conversion from parenteral to oral route and application of intravenous to oral switch over through case studies are exemplified.
Variants from the Diverse Virus Population Identified at Seroconversion of a Clade A Human Immunodeficiency Virus Type 1-Infected Woman Have Distinct Biological Properties

ABSTRACT Development of effective therapeutics to prevent new infections with human immunodeficiency type 1 (HIV-1) is predicated on an understanding of the properties that provide a selective advantage to a transmitted viral population. In contrast to the homogeneous virus population that typifies early HIV-1 infection of men, the viral population in women recently infected with clade A HIV-1 is genetically diverse, based on evaluation of the envelope gene. A longitudinal study of viral envelope evolution in several women suggested that representative envelope variants detected at seroconversion had distinct biological properties that affected viral fitness. To test this hypothesis, a full-length, infectious molecular clone, Q23-17, was obtained from an infected woman 1 year following seroconversion, and chimeric viruses containing envelope genes representative of seroconversion and 27-month-postseroconversion populations were constructed. Dendritic cells (DC) could transfer infection of seroconversion variant Q23ScA, which dominated the viral population in the year following seroconversion, and the closely related 1-year isolate Q23-17 to resting peripheral blood mononuclear cells (PBMC). In contrast, resting PBMC exposed to DC pulsed with Q23ScB, which was detected infrequently in samples after seroconversion, or the 27-month chimeras were inconsistently infected. Additionally, quiescent PBMC infected with Q23ScA or Q23-17 proliferated more robustly than uninfected cells or cells infected with the other envelope chimeras in response to immobilized anti-CD3. Stimulation with tetanus toxoid led to an increased proportion of CD45RA+ cells and a decreased expression of CD28 on CD45RO+ cells in cultures of Q23-17-infected PBMC. These data demonstrate that variants from the heterogeneous seroconversion clade A HIV-1 population in a Kenyan woman have distinct biological features that may influence viral pathogenesis.
Myoblast transplantation for inherited myopathies: a clinical approach

Myoblast transplantation (MT) is an experimental strategy for the potential treatment of myopathies. MT has two properties that make it potentially beneficial: genetic complementation and myogenic potential. Preclinical experiments on monkeys have shown that promising results can be obtained with MT in large muscles of primates depending on two conditions: appropriate immunosuppression and cell delivery by a method of high-density injections. Preclinical work on MT is being, or may be, addressed to: develop efficient methods of donor cell delivery applicable to clinics; control or avoid acute rejection by methods with the fewest secondary effects; understand the factors that condition the early survival of donor cells following transplantation; increase the success of each individual injection; re-engineer a functional structure in muscles that degenerates to fibrosis and fat substitution; and search for precursor cells with potential advantages over myoblasts.
Central fatigue affects plantar flexor strength after prolonged running

The primary aim of this study was to examine central fatigue of the plantar flexor muscle group after prolonged running using the twitch interpolation technique. Eight healthy, habitually active male subjects ran on a motorized treadmill for 2 h at a speed corresponding to 75% of peak oxygen uptake (VO2peak). Maximal voluntary isometric contraction (MVC) strength as well as the electrically induced twitch produced during MVC [interpolated twitch (IT)] and at rest [resting twitch (RT)] were measured before and after running. The level of activation (LOA) during each MVC was calculated as LOA (%)=100(1−IT/RT). Both MVC and LOA decreased (17±16% and 19±15%, respectively, P<0.05) after running, whereas RT did not change. The decrease in MVC was correlated with the decrease in LOA (r=0.87, P<0.05). The results demonstrate that after 2 h of treadmill running at an intensity of 75% of VO2peak, there was a reduction in maximal voluntary plantar flexor muscle strength that was mainly related to central fatigue.
Sperm penetration in parthenogenetic mouse embryos triggers a plasma membrane block to polyspermy

Summary Mouse oocytes activated parthenogenetically do not generate a plasma membrane block against spermatozoa over the first three cell cycles. We show that they lose this fusibility spontaneously at the 8-cell stage. Insemination of 1-cell parthenogenetic embryos induces loss of fusibility earlier, at the 2-cell stage. This observation suggests that incorporation of the sperm cell membrane components into the oolemma may be responsible for the development of the membrane block.
Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia

Low folate intake as well as alterations in folate metabolism as a result of polymorphisms in the enzyme methylenetetrahydrofolate reductase (MTHFR) have been associated with an increased incidence of neural tube defects, vascular disease, and some cancers. Polymorphic variants of MTHFR lead to enhanced thymidine pools and better quality DNA synthesis that could afford some protection from the development of leukemias, particularly those with translocations. We now report associations of MTHFR polymorphisms in three subgroups of pediatric leukemias: infant lymphoblastic or myeloblastic leukemias with MLL rearrangements and childhood lymphoblastic leukemias with either TEL-AML1 fusions or hyperdiploid karyotypes. Pediatric leukemia patients (n = 253 total) and healthy newborn controls (n = 200) were genotyped for MTHFR polymorphisms at nucleotides 677 (C→T) and 1,298 (A→C). A significant association for carriers of C677T was demonstrated for leukemias with MLL translocations (MLL+, n = 37) when compared with controls [adjusted odd ratios (OR) = 0.36 with a 95% confidence interval (CI) of 0.15–0.85; P = 0.017]. This protective effect was not evident for A1298C alleles (OR = 1.14). In contrast, associations for A1298C homozygotes (CC; OR = 0.26 with a 95% CI of 0.07–0.81) and C677T homozygotes (TT; OR = 0.49 with a 95% CI of 0.20–1.17) were observed for hyperdiploid leukemias (n = 138). No significant associations were evident for either polymorphism with TEL-AML1+ leukemias (n = 78). These differences in allelic associations may point to discrete attributes of the two alleles in their ability to alter folate and one-carbon metabolite pools and impact after DNA synthesis and methylation pathways, but should be viewed cautiously pending larger follow-up studies. The data provide evidence that molecularly defined subgroups of pediatric leukemias have different etiologies and also suggest a role of folate in the development of childhood leukemia.