Miracle-dz/UniFAR-FTUs huggingface dataset:
Managing the Pediatric Patient and the Adolescent/Adult Transition

Healthcare management of the developing child with hemophilia presents several difﬁculties. Determining the optimum medication dose is complicated by the difﬁculty of performing pharmacokinetic studies in children and the fact that extrapolation from data collected in adults is generally unsatisfactory. Even when pediatric pharmacokinetic data are available, accumulating evidence suggests that there can be wide interindividual differences; age and size are important contributing factors. Achieving the venous access necessary for blood factor administration is frequently difﬁcult in the small child. Preliminary results suggest that an arteriovenous ﬁstula may be an appropriate option in some patients. Finally, there is the question of whether prophylactic therapy should be discontinued as patients enter adulthood. This article provides insights for managing this challenging patient population.
The Role of Growth Factors and Cytokines during Implantation: Endocrine and Paracrine Interactions

Implantation, a critical step for establishing pregnancy, requires molecular and cellular events resulting in uterine growth and differentiation, blastocyst adhesion, invasion, and placental formation. Successful implantation requires a receptive endometrium, a normal and functional embryo at the blastocyst stage, and a synchronized dialogue between maternal and embryonic tissues. In addition to the well-characterized role of sex steroids, the complexity of embryo implantation and placentation is exempliﬁed by the number of cytokines and growth factors with demonstrated roles in these processes. Disturbances in the normal expression and action of these cytokines result in an absolute or partial failure of implantation and abnormal placental formation in mice and human. Members of the gp130 cytokine family, interleukin-11 (IL-11) and leukemia inhibitory factor, the transforming growth factor beta superfamily, the colony-stimulating factors, and the IL-1 and IL-15 systems are crucial molecules for a successful implantation. Chemokines are also important, both in recruiting speciﬁc cohorts of leukocytes to the implantation site and in trophoblast trafﬁcking and differentiation. This review provides discussion of the embryonic and uterine factors that are involved in the process of implantation in autocrine, paracrine, and/or juxtacrine manners at the hormonal, cellular, and molecular levels.
Role of Amantadine and Other Adjuvant Therapies in the Treatment of Hepatitis C

There is room for improvement in the treatment of chronic hepatitis C with standard interferon (IFN) alfa. In the search for treatment adjuvants, the antiviral compound ribavirin has been found to signiﬁcantly increase sustained virological response. Despite this improvement, the rate of ‘‘cure’’ remains low at approximately 40%, thus stimulating the search for additional adjuvants. In 1997, it was suggested that amantadine monotherapy could be used successfully to treat patients with chronic hepatitis C who had previously failed IFN alfa therapy, but ensuing studies could not support these ﬁndings. Instead, researchers have studied amantadine as an adjuvant to either IFN alfa alone or IFN alfa plus ribavirin, and promising results have been published. In this article, the author reviews the role of amantadine alone or as part of combination therapy regimens for chronic hepatitis C and brieﬂy looks at the use of other agents as potential adjuvants.
Management of Hepatitis B in Liver Transplantation Patients

The success of orthotopic liver transplantation for patients with hepatitis B virus (HBV) disease has been compromised by reinfection. Prophylaxis has dramatically lowered the rate of reinfection and increased patient survival. Long-term treatment with hepatitis B immunoglobulin (HBIg), although expensive, is effective. New antiviral nucleoside analogs have also been evaluated. In patients with cirrhosis and replicative HBV infection, lamivudine before transplantation and in combination with HBIg post transplantation reduces reinfection, but the rate of resistance mutation is rather high, reaching 25% at 2 years. Adefovir has been used as a rescue therapy and prior to transplantation in lamivudine-resistant patients, signiﬁcantly improving liver function and reducing HBV DNA levels. Patients with active viral replication should receive preoperative antiviral therapy with lamivudine. HBIg therapy may be discontinued in selected patients after transplantation, albeit with caution, because low levels of HBV DNA have persisted. Antiviral therapy has improved the prognosis after graft infection.
An Update on the Prevalence and Characterization of H-PF4 Antibodies in Asian-Indian Patients

Heparin is the second most widely used anticoagulant/antithrombotic agent besides warfarin and is commonly used for various purposes such as treatment and surgical indications. A signiﬁcant adverse effect of heparin treatment can occur when heparin binds platelet factor 4 (H-PF4) to form a complex that results in formation of H-PF4 antibodies, which in turn leads to platelet/endothelial cell activation followed by heparin-induced thrombocytopenia (HIT). Based on the heparin-induced platelet aggregation and enzyme-linked immunosorbent assay tests, the H-PF4 antibody (HIT antibody) was diagnosed in 6% of Indian patients undergoing cardiovascular surgery who received unfractionated heparin, but the frequency of occurrence rose to 15% when the patients were tested with the 14 C-serotonin release assay. This highlights some methodological variations in the diagnosis of HIT antibodies. It was also found that all the HIT-positive patients were either homozygous or heterozygous for the Fc g RIIa polymorphism, which also highlights the role of this polymorphism in the occurrence of HIT. Very recent studies show that increases in HIT antibody production may also be due to heparin contaminants. Although these antibodies do not result in thrombocytopenia, contaminants in heparin may be capable of triggering a differential immunogenic response in comparison with contami-nant-free heparin. Here we discuss the methodological differences in diagnosing HIT, the potential impact of contaminants in heparin, as well as future considerations.
Genetic Predisposition to Gallbladder Stones

Geographic and ethnic differences in gallstone prevalence rates and familial clustering of cholelithiasis imply that genetic factors inﬂuence the risk of gallstone formation. Recently, twin, family, and linkage studies conﬁrmed a genetic predisposition to the development of symptomatic gallstones. In rare instances, mutations in single genes confer a substantial risk for the formation of gallstones. However, in the majority of cases gallstones might develop as a result of lithogenic polymorphisms in several genes and their interactions with multiple environmental factors, rendering gallstones generally a complex genetic disorder. Some of the rare monogenic forms of cholelithiasis were unraveled but the lithogenic genes that increase the susceptibility to cholelithiasis in the majority of gallstone carriers remain elusive. Identiﬁcation of these lithogenic genes will provide novel means of risk assessment, strategies for prevention, and targets for nonsurgical management of cholelithiasis, which currently is one of the most expensive digestive disorders.
Formation of Ni3InGaAs phase in Ni/InGaAs contact at low temperature

The composition and morphology of the product phase after the reaction of Ni thin film with In0.53Ga0. 47As substrate at 350 °C were investigated by atom probe tomography, X-ray diffraction, and scanning electron microscopy. Results show the formation of a unique Ni3(In0.53Ga0.47)As phase with a low concentration in-depth gradient of Ni and the decoration of the grain boundaries by In atoms. These analyses indicate that Ni is the main diffusing specie during the growth of Ni3(In0.53Ga0.47)As phase. The volume of the product phase is higher than the volume of the consumed Ni film as expected for the formation of Ni3(In0.53Ga0.47)As phase.
Slow-wave sleep : generation and propagation of slow waves, role in long-term plasticity and gating

Sleep is known to mediate several major functions in the brain and among them are the gating of sensory information during sleep and the sleep-related improvement in memory consolidation. Slow-wave sleep in particular is thought to be critical for both of these processes. However, their physiological mechanisms are unknown. Also, the electrophysiological hallmark of slow-wave sleep is the presence of large amplitude slow waves in the cortical local field potential and the alternation of periods of intense synaptic activity in which cortical neurons are depolarized and fire action potentials and periods of silence in which no firing occurs, cortical neurons are hyperpolarized, and very little synaptic activities are observed. First, in order to better understand the studies presented in this manuscript, a general introduction covering the thalamocortical system architecture and function is presented, which includes a description of the states of vigilance, followed by a description of the rhythms present in the thalamocortical system during slow-wave sleep, then by a description of the mechanisms of synaptic plasticity, and finally two hypotheses about how sleep might affect the consolidation of memory are presented. Then, three studies are presented and were designed to characterize the properties of the sleep slow oscillation. In the first study (Chapter II), we showed that periods of activity (and silence) occur almost synchronously in neurons that are separated by up to 12 mm. The activity was initiated in a focal point and rapidly propagated to neighboring sites. Surprisingly, the onsets of silent states were even more synchronous than onsets of active states. The working hypothesis for the second study (Chapter III) was that active states are generated by a summation of spontaneous mediator releases. Using different recordings in both anesthetized and non-anesthetized animals, we showed that no neuronal firing occurs in the neocortex during silent states of slow-wave sleep but some synaptic activities might be observed prior to the onset of active states, which was in agreement with our hypothesis. We also showed that layer V neurons were leading the onset of active states in most of the cycles but this would be due to probabilistic reasons; these cells being equipped with the most numerous synaptic contacts among cortical neurons. We also showed that slow-wave sleep and ketamine-xylazine shares many similarities.
Who Is at High Risk for Lung Cancer? Population-Level and Individual-Level Perspectives

Lung cancer is the leading cause of cancer death in the world. However, there is large geographic variation internationally and within nations. Despite the fact that many causes of lung cancer have been established, cigarette smoking is the principal cause. Accounting for historical prevalence of cigarette smoking is a useful predictor of the lung cancer burden in most populations. The populations at high present risk of lung cancer can usually be predicted based on historical patterns of the prevalence of cigarette smoking, and the high-risk populations of the future can be predicted based on the current prevalence of cigarette smoking. Lung cancer rates are consistently higher among men than women and are particularly high among African American men and among those of lower socioeconomic status. At the individual level, some segments of the population (e.g., African Americans, females) have been hypothesized to have greater susceptibility to lung cancer for a given degree of cigarette smoking. Common variants in genes that encode for enzymes involved in carcinogen metabolism and detoxiﬁcation and in repairing DNA damage are likely to be important determinants of interindividual susceptibility to smoking-caused lung carcinogenesis. Many lung cancer risk factors have been identiﬁed, but active cigarette smoking is the predominant cause of lung cancer and the principal marker of both high-risk populations and high-risk individuals. In the absence of cigarette smoking, lung cancer would be a rare disease. Strategies that effectively prevent youths from starting to smoke and that promote cessation among dependent smokers can transform populations from high risk to low risk.
ICSI: Where We Have Been and Where We Are Going

Notwithstanding the broad success of in vitro fertilization (IVF), a failure to achieve fertilization still plagues a substantial group of patients, with sperm abnormalities the main culprit. In the 1980s, several micromanipulation procedures were adopted from animal husbandry to facilitate gamete interaction, and this resulted in the development of intracytoplasmic sperm injection (ICSI), a procedure through which an oocyte can be fertilized independently of the morphology and/or motility of the single spermatozoon injected. The procedure was ﬁrst used in cases of fertilization failure after standard IVF or when an inadequate number of sperm cells were available. The consistency of fertilization independent of the functional quality of the spermatozoon has extended the application of ICSI to immature spermatozoa retrieved surgically from the epididymis and testis. Moreover, the need to denude the oocyte has allowed assessment of the nuclear maturity of the oocyte. ICSI is also preferred in conjunction with preimplantation genetic diagnosis and recently has been used to treat HIV discordant couples, where there is a pressing need to minimize the exposure of the oocyte to a large number of spermatozoa. For all ages and with all the different sperm types used, fertilization after ICSI is at (cid:1) 70 to 80% and it ensures a clinical pregnancy rate of up to 45%. These results have made ICSI a procedure comparable in popularity with IVF and have minimized the need for couples suffering from all forms of male infertility to resort to adoption or the use of donor sperm.
Molecular Mechanisms of Treatment Resistance in Endometriosis: The Role of Progesterone–Hox Gene Interactions

HOX genes, encoding homeodomain transcription factors, are dynamically expressed in endometrium, where they are necessary for endometrial growth, differentiation, and implantation. In human endometrium, the expression of HOXA10 and HOXA11 is driven by sex steroids, with peak expression occurring at time of implantation in response to rising progesterone levels. However, the maximal HOXA10 and HOXA11 expression fails to occur in women with endometriosis. In endometriosis, altered progesterone receptor expression or diminished activity may lead to attenuated or dysregulated progesterone response and decreased expression of progesterone-responsive genes including HOX genes in the eutopic endometrium. In turn, other mediators of endometrial receptivity that are regulated by HOX genes, such as pinopodes, a v b 3 integrin, and IGFBP-1, are downregulated in endometriosis. HOXA10 hypermethylation has recently been demonstrated to silence HOXA10 gene expression and account for decreased HOXA10 in the endometrium of women with endometriosis. Silencing of progesterone target genes by methylation is an epigenetic mechanism that mediates progesterone resistance. The relatively permanent nature of methylation may explain the widespread failure of treatments for endometriosis-related infertility.
Estradiol Is a Potent Protective, Restorative, and Trophic Factor after Brain Injury

Estrogens are a group of pleiotropic steroid hormones that exhibit diverse mechanisms of action in multiple physiologic systems. Over the past 30 years, biomedical science has begun to appreciate that endogenous estrogens and their receptors display important roles beyond the reproductive system. Our growing appreciation of novel, nonreproductive functions for estrogens has fundamentally contributed to our knowledge of their role in human health and disease. Recent ﬁndings from the Women’s Health Initiative have caused clinicians and scientists to question whether estrogens are protective factors or risk factors. In light of the dichotomy between basic science and clinical studies, this review will attempt to reconcile differences between them. We will focus on studies from our laboratory and others highlighting the beneﬁcial properties of the most abundant endogenous estrogen, 17 b -estradiol, using in vivo and in vitro models of cerebral ischemia and neuronal injury. These studies demonstrate that 17 b -estradiol powerfully protects the brain using multiple molecular mechanisms that promote: (1) decreased cell death, (2) increased neurogenesis, (3) an enhancement of neurotrophic support, and (4) the suppression of proinﬂammatory pathways.
Corticosteroid Therapy in Patients with Severe Sepsis and Septic Shock

Corticosteroids have been considered for decades for the treatment of severe sepsis and septic shock, based on their pivotal role in the stress response and their hemodynamic and antiinﬂammatory effects. Whereas short-term therapy with high doses of corticosteroids (up to 42 g hydrocortisone equivalent for 1–2 days) has been ineffective or potentially harmful, prolonged therapy with lower doses (200–300 mg hydrocortisone for 5–7 days or longer) in septic shock has recently revealed beneﬁcial effects in several randomized, controlled trials. Assuming relative adrenal insufﬁciency (RAI) and peripheral cortisol resistance, treatment with low-dose hydrocortisone improved shock reversal, reduced inﬂammation, and improved outcome. Shock reversal and reduction of mortality were more effective in patients with RAI, and most signiﬁcant in patients with severe shock. Diagnosis of RAI with corticotropin tests in septic shock, however, is highly dependent on cut-off values and deﬁnition of RAI. Thus, it is not clear yet which patients beneﬁt most from low-dose hydrocortisone and if treatment should be restricted to patients with RAI. In addition the role of ﬂudrocortisone is uncertain. Nevertheless, based on current data, low-dose hydrocortisone therapy should deﬁnitely be considered in vasopressor-dependent septic shock. This review will address some critical points.
Resonant damping of kink oscillations of thin cooling and expanding coronal magnetic loops

We have considered resonant damping of kink oscillations of cooling and expanding coronal magnetic loops. We derived an evolutionary equation describing the dependence of the oscillation amplitude on time. When there is no resonant damping, this equation reduces to the condition of conservation of a previously derived adiabatic invariant. We used the evolutionary equation describing the amplitude to study the competition between damping due to resonant absorption and amplification due to cooling. Our main aim is to investigate the effect of loop expansion on this process. We show that the loop expansion acts in favour of amplification. We found that, when there is no resonant damping, the larger the loop expansion the faster the amplitude growths. When the oscillation amplitude decays due to resonant damping, the loop expansion reduces the damping rate. For some values of parameters the loop expansion can fully counterbalance the amplitude decay and turn the amplitude evolution into amplification.
Comparison of Recombinant Human Thrombin and Plasma-Derived Human α-Thrombin

Bleeding can be a serious complication of surgery, and topical thrombin is widely used as an adjunct to hemostasis in diverse surgical settings. The potent hemostatic properties of thrombin derive from its ability to activate platelets directly to aggregate and adhere to damaged vessels and to catalyze the formation simultaneously of a ﬁbrin matrix. Application of exogenous thrombin bypasses the physiological process of generating a thrombin burst by directly initiating the terminal reactions of blood clot formation. Currently, thrombin used to control surgical bleeding is primarily from bovine plasma, with a small percentage from human plasma. Human thrombin isolated from pooled plasma carries the risk of transmitting plasma-borne pathogens or prion diseases. The bovine preparations have been associated with protein and preparative contaminants that pose potential risks of developing cross-reacting antibodies. There is a need for a pure therapeutic preparation of human thrombin. Recombinant human thrombin (rhThrom-bin) has been efﬁciently produced from a prethrombin-1 precursor obtained from Chinese hamster ovary cell culture. This rhThrombin is substantially free of process-derived contaminants and has been characterized extensively in terms of composition, primary, secondary, and tertiary structure, enzymatic activity; and in vivo pharmacology. In vivo studies of topically applied rhThrombin have shown it is effective in achieving hemostasis in a rabbit liver excisional wound model. Clinical studies are ongoing to evaluate the safety and efﬁcacy of rhThrombin as an adjunct to hemostasis in patients undergoing surgery.
Using Narrative as a Bridge: Linking Language Processing Models with Real-Life Communication

In chronic aphasia, maximizing generalization of improved language abilities from clinical tasks to everyday communication can require the same systematic planning process as the early stages of therapy, often drawing on additional areas of knowledge and successes from other clinical populations. The use of narrative structure is shown here to be a useful framework for building on the developments within sentence processing impairments in aphasia and creating a bridge to more real-life language tasks. An intervention based on narrative structure is described with two people with different language proﬁles and at different stages of the chronic aphasia spectrum. The insights gained in assessing language ability, underpinning intervention, and capturing therapeutic changes are demonstrated.
MR Imaging of the Forefoot: Morton Neuroma and Differential Diagnoses

Magnetic resonance (MR) imaging of Morton neuromas is highly accurate. Morton neuromas are more conspicuous when the patient is prone positioned and the foot is plantar ﬂexed than in the supine position with the toes pointing upward. MR imaging of Morton neuromas has a large inﬂuence on the diagnostic thinking and treatment plan of orthopedic foot surgeons. The most common differential diagnoses include intermetatarsal bursitis, stress fractures, and stress reactions. Some diagnoses (nodules associated with rheumatoid arthritis, synovial cyst, soft tissue chondroma, and plantar ﬁbromatosis) are rare and can be diagnosed with histologic correlation only