Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of a method of preparation of lipid emulsions as a model for chylomicron-like particles

Abstract Chylomicron remnants can penetrate into the artery wall, where they can initiate atherogenesis. Since it is difficult to isolate these particles from human blood because of contamination with other lipoproteins, the use of lipid emulsions as chylomicron remnant-like particles (CRLPs) has been proposed to study their metabolism. This study was aimed to evaluate the methodology for the preparation of CRLP. Artificial chylomicrons were prepared by sonication of a lipid mixture and separated by density gradient centrifugation. Lipid classes were analyzed by HPLC and fatty acids by GC. Particle size was measured by dynamic light scattering and the presence of apolipoprotein E by immunoblotting. The highest lipid content was found in the 60 < Sf < 400 fraction (Sf = Svedberg flotation rate), followed by the Sf > 400. This latter fraction presented the highest triacylglycerol (TAG) concentration, which was dramatically reduced in the 20 < Sf < 60 fraction. Fatty acid composition in TAG and phospholipids resembled that of the standards used with little modifications. The repeatability of the method was excellent, showing relative standard errors below 10%. The mean size of the 60 < Sf < 400 and Sf > 400 fractions, was 195.1 and 347.8 nm, respectively. The lipid analysis showed that Sf > 400 particles resembled the composition of natural chylomicrons and the 60 < Sf < 400 particles that of chylomicron remnants, the range of particle size being more homogeneous in the 60 < Sf < 400 fraction. The method mentioned in this article is not only a reliable method for the preparation of CRLP, but also for native chylomicron-like particles, in terms of lipid composition and particle size.
Is The “See and Treat” Approach Appropriate for Management of Women with Abnormal Cervical Cytology in Thailand?

At present, the “see and treat” approach for women with abnormal cervical cytology is widely accepted. It has been proven to be more cost-effectiveness than conventional management, making it particularly attractive for many regions in Thailand where resources are limited and poor patients’ compliance is expected. However, the main disadvantage of the “see and treat” approach is the risk of overtreatment. National Health Service (NHS) guidelines recommend that the overtreatment rate in the “see and treat” approach must be less than 10%. The overtreatment rate appears to be acceptable if the “see and treat” approach is carried out in women with high-grade squamous intraepithelial lesion (HSIL) cytology or in women with lesser grades of smear abnormality whose colposcopic findings suggest high-grade disease.
Targeting insulin sensitivity in the treatment of polycystic ovary syndrome

Targeting insulin resistance may result in a list of benefits for women with PCOS, including hormonal, metabolic and ovulatory (and fertility) improvements. The therapeutic strategy to treat PCOS should however depend on the clinical situation, the phenotype, the degree of androgen excess, age, the presence of infertility and the woman's desire to conceive, the presence of obesity and, finally, the spectrum of metabolic abnormalities and the need to treat or prevent long-term associated comorbidities. According to the needs, therapeutic options include, alone or in combination, lifestyle management, particularly in the presence of obesity, the use of insulin sensitizers, metformin and thiazolidinediones, antiandrogens or estro-progestins.
Enhancing mTOR-targeted cancer therapy

Background: The mammalian target of rapamycin (mTOR) has emerged as an attractive cancer therapeutic target. Accordingly, several mTOR inhibitors (e.g., rapamycin and its analogs; rapalogs) are currently being tested in many cancer clinical trials. Despite the encouraging results showing that some rapalogs improved overall survival among patients with metastatic renal-cell carcinoma, the single-agent activity of rapalogs in most other tumor-types has been modest, at best. Objective: To review the current understanding of the mTOR axis and discuss potential strategies to enhance mTOR-targeted cancer therapy. Methods: Preclinical and clinical data in peer-reviewed reports on the novel biological and therapeutic parts of the mTOR axis are discussed. Conclusion: The mTOR axis involves complex regulatory networks. Inhibition of the mTOR axis with a rapalog induces feedback activation of several survival signaling pathways such as Akt activation, which, in turn, blunt rapalogs' anticancer efficacy. Thus, blockage or prevention of the activation of these survival signaling pathways may enhance mTOR-targeted cancer therapy.
Profile of the shared care activities of mental health teams in Ireland

In order to facilitate recovery within the community and provide service users with a continuum of care, a high degree of coordination and collaboration is needed between primary care teams and secondary care mental health teams. In 2012 the HSE National Vision for Change Advancing the Shared Care Approach between Primary Care and Specialist Mental Health Services made a number of recommendations on delivering effective shared care. Using a survey method, the current research aimed to examine the extent to which mental health teams in the Republic of Ireland were achieving these recommendat ions.
Intracellular immune dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome: state of the art and therapeutic implications

Background: Evidence in support of intracellular immune dysfunctions in people with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is accumulating, but few studies have addressed intracellular immunity as a potential therapeutic target. Objective: To provide an overview of our present understanding of intracellular immunity in ME/CFS, to relate the intracellular immune dysfunctions to other aspects of the illness like decreased natural killer cell function, the presence of infections and poor exercise performance, and to point to potential therapeutic targets. Methods: An in-depth review of the scientific literature of intracellular immunity in people with ME/CFS was performed. Results/conclusion: From the scientific literature it is concluded that proteolytic cleavage of the native RNase L enzyme is characteristic of the dysregulation of intracellular immunity in people with ME/CFS, but the origin of the dysregulation is speculative. There is increasing evidence for immune cell apoptosis and upregulation of various aspects of the 2′-5′ oligoadenylate (2-5A) synthetase/RNase L pathway in ME/CFS. This review provides the theoretical rationale for conducting studies examining the effectiveness of direct or indirect drug targeting of the 2-5A synthetase/RNase L pathway in ME/CFS patients.
Spinal cord excitability is not influenced by elevated blood lactate levels

The aim of the present study was to examine the association of high blood lactate levels, induced with a maximal cycling or with an intravenous infusion, with spinal cord excitability. The study was carried out on 17 male athletes; all the subjects performed a maximal cycling test on a mechanically braked cycloergometer, while 6 of them were submitted to the intravenous infusion of a lactate solution (3 mg/kg in 1 min). Before the exercise or the injection, also at the end as well as 5 and 10 min after the conclusion, venous blood lactate was measured and excitability of the spinal α-motoneurons was evaluated by using the H reflex technique. In both experimental conditions, it has been observed that an exhaustive exercise is associated with a strong increase of blood lactate (but not of blood glucose) and with a significant reduction of spinal excitability. Since a similar augment of blood lactate induced by an intravenous infusion, in subjects not performing any exercise, is not associated with significant changes of spinal excitability, it can be concluded that the increase of blood lactate levels during a maximal exercise is not per se capable of modifying the excitability of spinal α-motoneurons.
Critical care issues in solid organ injury: Review and experience in a tertiary trauma center

Background and Aim: Solid organ (spleen and liver) injuries are dreaded by both surgeons and anesthesiologists because of associated high morbidity and mortality. The purpose of this review is to describe our experience of critical care concerns in solid organ injury, which otherwise has been poorly addressed in the literature. Materials and Methods: Retrospective cohort of solid organ injury (spleen and liver) patients was done from January 2010 to December 2011 in tertiary level trauma Center. Results: Out of 624 abdominal trauma patients, a total of 212 patients (70%) were admitted in intensive care unit (ICU). Their ages ranged from 6 to 74 years (median 24 years). Nearly 89% patients in liver trauma and 84% patients in splenic trauma were male. Mechanism of injury was blunt abdominal trauma in 96% patients and the most common associated injury was chest trauma. Average injury severity score, sequential organ failure assessment, lactate on admission was 16.84, 4.34 and 3.42 mmol/L and that of dying patient were 29.70, 7.73 and 5.09 mmol/L, respectively. Overall mortality of ICU admitted solid organ injury was 15.55%. Major issues of concern in splenic injury were hemorrhagic shock, overwhelming post-splenectomy infection and post-splenectomy vaccination. Issues raised in liver injury are damage control surgery, deadly triad, thromboelastography guided transfusion protocols and hemostatic agents. Conclusions: A protocol-based and multidisciplinary approach in high dependency unit can significantly reduce morbidity and mortality in patients with solid organ injury.
Intrinsic properties of and thalamocortical inputs onto identified corticothalamic-VPM neurons

Abstract Corticothalamic (CT) feedback plays an important role in regulating the sensory information that the cortex receives. Within the somatosensory cortex layer VI originates the feedback to the ventral posterior medial (VPM) nucleus of the thalamus, which in turn receives sensory information from the contralateral whiskers. We examined the physiology and morphology of CT neurons in rat somatosensory cortex, focusing on the physiological characteristics of the monosynaptic inputs that they receive from the thalamus. To identify CT neurons, rhodamine microspheres were injected into VPM and allowed to retrogradely transport to the soma of CT neurons. Thalamocortical slices were prepared at least 3 days post injection. Whole-cell recordings from labeled CT cells in layer VI demonstrated that they are regular spiking neurons and exhibit little spike frequency adaption. Two anatomical classes were identified based on their apical dendrites that either terminated by layer V (compact cells) or layer IV (elaborate cells). Thalamic inputs onto identified CT-VPM neurons demonstrated paired pulse depression over a wide frequency range (2–20 Hz). Stimulus trains also resulted in significant synaptic depression above 10 Hz. Our results suggest that thalamic inputs differentially impact CT-VPM neurons in layer VI. This characteristic may allow them to differentiate a wide range of stimulation frequencies which in turn further tune the feedback signals to the thalamus.
Therapeutic Update on the Prevention and Treatment of Venous Thromboembolism

Venous thromboembolism (VTE) is a common condition that increases in incidence with age and risk factors. Therapies for VTE are aimed at either preventing the disease in high-risk individuals or treating patients who have developed VTE. Assessing risk and aggressively using the recommended therapies is primacy in preventing VTE in surgical and medical patients. Risk of VTE in medical patients has become more defined in recent years, and prophylaxis in this group can prevent scores of iatrogenic VTE. Treatment of VTE has evolved in the past decade from a condition that required hospitalization for 5 to 7 days to a disease state that can be conveniently and safely treated on an outpatient basis, largely due to the advent of low-molecular-weight heparins and patient self-directed treatment.
The kinase NIK as a therapeutic target in multiple myeloma

Introduction: Multiple myeloma (MM) is a neoplasm derived from B lymphocytes and often results in uncontrolled clonal expansion of antibody-secreting cells. While current treatments are able to prolong survival, MM remains incurable. Excessive NF-κB activity in MM contributes to tumor progression and survival. Areas covered: The contribution of NF-κB-inducing kinase (NIK) to alternative NF-κB signaling, where it is the key kinase, and classical NF-κB signaling. Modulation of NIK by natural and chemical factors and current and potential therapies for MM that target NIK. Expert opinion: Mutations affecting the activation of NIK have been identified in MM samples and cell lines, suggesting that NIK may be an important target for therapy of MM. NIK contributes to activation of both NF-κB pathways in MM, giving us the opportunity to limit two pathways contributing to oncogenic survival with a single therapeutic. Many of the mutations identified in MM cells result in the same outcome, hyperactive NIK, thus a single therapeutic may be effective in many patients even though they carry differing mutations. As NIK appears only to activate classical NF-κB when overexpressed, and in normal cells NIK levels are usually low, it is possible that therapeutics designed to limit the amount of NIK may not produce serious side effects in healthy cells.
Effect of low dose tranexamic acid on intra-operative blood loss in neurosurgical patients

Background: Blood loss is often a major complication in neurosurgery that requires transfusion of multiple units of blood. The purpose of this study was to assess the effect of tranexamic acid (TXA) on intraoperative blood loss and the need for blood transfusion in patients undergoing craniotomy for tumor excision. Materials and Methods: A total of 100 patients aged 18-60 years, with American Society of Anesthesiologists physical Status 1 and 2 scheduled to undergo elective craniotomy for tumor excision were enrolled. Patients received 10 mg/kg bolus about 20 min before skin incision followed by 1 mg/kg/h infusion of either TXA or saline. Hemodynamic variables, intravenous fluid transfused, amount of blood loss and blood given were measured every 2 h. Laboratory parameters such as serum electrolytes and fibrinogen values were measured every 3 h. On the 5 th postoperative day hemoglobin (POD Hb5), Hb estimation was done and the estimated blood loss (EBL) calculated. Patients were also monitored for any complications. Results: The Mean heart rate in TXA group was significantly lower compared with the saline group. Mean arterial pressure and fibrinogen levels were higher in TXA group. The mean total blood loss in the TXA group was less than in the saline group. Blood transfusion requirements were comparable in two groups. The EBL and POD5 Hb were comparable in two groups. Conclusion: Even though, there is a significant reduction in the total amount of blood loss in TXA group. However, there was no reduction in intraoperative transfusion requirement.
Quantitative analysis of somatosensory cortex development in metatherians and monotremes, with comparison to the laboratory rat

Abstract Metatherians and monotremes are born in an immature state, followed by prolonged nurturing by maternal lactation. Quantitative analysis of isocortical sections held in the collections at the Museum für Naturkunde, Berlin was used to compare the pace of somatosensory cortex development relative to body size and pallial thickness between metatherian groups, monotremes, and the laboratory rat. Analysis indicated that the pace of pallial growth in the monotremes is much lower than that in the metatherians or laboratory rat, with an estimated 8.6-fold increase in parietal cortex thickness between 10 and 100 mm body length, compared to a 10- to 20-fold increase among the metatherians and the rat. It was found that aggregation of cortical plate neurons occurs at similar embryo size in the mammals studied (around 8–14 mm body length) and a similar pallial thickness (around 200 µm), but that proliferative zone involution occurs at a much higher body size and pallial thickness in the monotremes compared to the metatherians and the laboratory rat. The observations suggest that cortical development in the monotremes is slower and subject to different regulatory signals to the therians studied. The slow pace may be related to either generally slower metabolism in monotremes or less efficient nutrient supply to the offspring due to the lack of teats.
Dexmedetomidine as an adjuvant to ropivacaine in supraclavicular brachial plexus block

Context: Dexmedetomidine as an adjuvant to local anesthetics in peripheral nerve blocks has been used in only a few studies. Aims: We aimed at assessing the effect of dexmedetomidine as an adjuvant to ropivacaine in supraclavicular brachial plexus block. Settings and Design: Random, controlled, and triple blind. Materials and Methods: Sixty American Society of Anesthesiologist grade I and II patients of either sex scheduled for elective upper limb surgery under supraclavicular brachial plexus block were divided into three equal groups in a prospective randomized double-blind controlled manner. For block patients in Group C received 0.5% ropivacaine (30cc), 0.5% ropivacaine with 50 μg dexmedetomidine (30cc) in Group D and 0.5% ropivacaine (30cc) in Group D-IV along with intravenous infusion of 50 μg dexmedetomidine in normal saline. Statistical Analysis Used: IBM-SPSS software version 17, Chi-square test, Mann-Whitney U-test. Results: Demographic profile and surgical characteristics were similar in all the three groups. Sensory block and motor block onset was earlier in group D than in group D-IV and group C. The sensory block and motor block duration was also prolonged in group D when compared with group D-IV and group C. The duration of analgesia was significantly longer in group D and D-IV when compared to group C. Conclusions: Dexmedetomidine as an adjuvant to 0.5%ropivacaine in ultrasound guided brachial plexus block shortens the sensory as well as motor block onset time, prolongs sensory and motor block duration and also increases the duration of analgesia. The action of dexmedetomidine most probably is local rather than centrally mediated.
Targeting ligand-operated chaperone sigma-1 receptors in the treatment of neuropsychiatric disorders

Introduction: Current drugs for the treatment of psychiatric or neurodegenerative disorders have limitations. Psychotherapeutic drugs such as typical and atypical antipsychotics, tricyclic antidepressants and selective monoamine reuptake inhibitors, aim to normalize the hyper- or hypo-neurotransmission of monoaminergic systems. Despite their contribution to the outcomes of psychiatric patients, these agents often exert severe side effects and require chronic treatments to promote amelioration of symptoms. Drugs available for the treatment of neurodegenerative disorders are severely limited. Areas covered: Recent evidence that has shed light on sigma-1 receptor ligands, which may serve as a new class of antidepressants or neuroprotective agents. Sigma-1 receptors are novel ligand-operated molecular chaperones regulating signal transduction, ER stress, cellular redox, cellular survival and synaptogenesis. Selective sigma-1 receptor ligands exert rapid antidepressant-like, anxiolytic, antinociceptive and robust neuroprotective actions in preclinical studies. Recent studies that suggest that reactive oxygen species might play a role as signal integrators downstream of Sig-1Rs are also covered. Expert opinion: The advances in sigma receptor research in the last decade have begun to elucidate the intracellular signal cascades upstream and downstream of sigma-1 receptors. The novel ligand-operated properties of the sigma-1 receptor chaperone may enable interventions by which stress-related cellular systems can be pharmacologically controlled.
Comparison of esmolol and labetalol, in low doses, for attenuation of sympathomimetic response to laryngoscopy and intubation

Objective: The present study compared the efficacy of esmolol and labetalol, in low doses, for attenuation of sympathomimetic response to laryngoscopy and intubation. Design: Prospective, randomized, placebo controlled, double-blinded study. Setting: Operation room. Patients and Methods: 75 ASA physical status I and II adult patients, aged 18-45 years undergoing elective surgical procedures, requiring general anesthesia and orotracheal intubation. Interventions: Patients were allocated to any of the three groups (25 each)-Group C (control)10 ml 0.9% saline i.v. Group E (esmolol) 0.5 mg/kg diluted with 0.9% saline to 10 ml i.v. Group L (labetalol) 0.25 mg/kg diluted with 0.9% saline to 10 ml i.v. In the control group 10 ml of 0.9% saline was given both at 2 and 5 min prior to intubation. In the esmolol group 0.5 mg/kg of esmolol (diluted with 0.9% saline to 10 ml) was given 2 min prior and 10 ml of 0.9% saline 5 min prior to intubation. In the labetalol group 10 ml of 0.9% saline was administered 2 min prior and 0.25 mg/kg of labetalol (diluted with 0.9% saline to 10 ml) 5 min prior to intubation. All the patients were subjected to the same standard anesthetic technique. Measurements: Heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded prior to induction, at time of intubation and 1, 3, 5, and 10 min after intubation. Mean arterial pressure (MAP) and rate pressure product (RPP) were calculated. Abnormal ECG changes were also recorded. Results: Compared to placebo and esmolol (0.5 mg/kg), labetalol (0.25 mg/kg) significantly attenuated the rise in heart rate, systolic blood pressure, and RPP during laryngoscopy and intubation. However, the difference was not statistically significant among the values for DBP and MAP. Conclusion: In lower doses, labetalol (0.25 mg/kg) is a better agent than esmolol (0.5 mg/kg) in attenuating the sympathomimetic response to laryngoscopy and intubation.
The role of myelin oligodendrocyte glycoprotein in autoimmune demyelination: a target for multiple sclerosis therapy?

Introduction: Myelin oligodendrocyte glycoprotein (MOG) is a myelin antigen at the outer surface of the central nervous system (CNS) myelin sheath, which may trigger T-cell as well as B-cell responses. It therefore constitutes a pivotal target for autoimmune responses, which result in inflammation and also demyelination in the CNS. In particular, it is a major target for auto-antibodies in experimental autoimmune encephalomyelitis (EAE), which mimics many aspects of multiple sclerosis (MS). B-cell responses toward MOG and anti-MOG antibodies have also been demonstrated in patients with demyelinating diseases, such as MS and acute disseminating encephalomyelitis (ADEM). Co-transfer of such anti-MOG antibodies in experimental models results in a distinct lesion pattern with antibody and complement-mediated demyelination, which is also hallmark of some lesion subtypes in MS. Areas covered: A comprehensive literature search on MOG, B cells, MS, and ADEM was performed to outline the role of MOG in autoimmune demyelination in animal models and its relevance for human disease. Expert opinion: Although the definite role of MOG in the pathogenesis of MS still remains to be clarified, innovative therapeutic strategies targeting B cells may reduce pathogenic immune responses against myelin auto-antigens including anti-myelin auto-antibodies.