Miracle-dz/UniFAR-FTUs huggingface dataset:
Estrogen receptor α, not β, is a critical link in estradiol-mediated protection against brain injury

Estradiol protects against brain injury, neurodegeneration, and cognitive decline. Our previous work demonstrates that physiological levels of estradiol protect against stroke injury and that this protection may be mediated through receptor-dependent alterations of gene expression. In this report, we tested the hypothesis that estrogen receptors play a pivotal role in mediating neuroprotective actions of estradiol and dissected the potential biological roles of each estrogen receptor (ER) subtype, ERα and ERβ, in the injured brain. To investigate and delineate these mechanisms, we used ERα-knockout (ERαKO) and ERβ-knockout (ERβKO) mice in an animal model of stroke. We performed our studies by using a controlled endocrine paradigm, because endogenous levels of estradiol differ dramatically among ERαKO, ERβKO, and wild-type mice. We ovariectomized ERαKO, ERβKO, and the respective wild-type mice and implanted them with capsules filled with oil (vehicle) or a dose of 17β-estradiol that produces physiological hormone levels in serum. One week later, mice underwent ischemia. Our results demonstrate that deletion of ERα completely abolishes the protective actions of estradiol in all regions of the brain; whereas the ability of estradiol to protect against brain injury is totally preserved in the absence of ERβ. Thus, our results clearly establish that the ERα subtype is a critical mechanistic link in mediating the protective effects of physiological levels of estradiol in brain injury. Our discovery that ERα mediates protection of the brain carries far-reaching implications for the selective targeting of ERs in the treatment and prevention of neural dysfunction associated with normal aging or brain injury.
Follicular thyroid carcinoma

: Follicular thyroid cancer is the second most common thyroid malignancy. This tumor has a predisposition for hematogenous dissemination an extra thyroid spread. Accurate cytological diagnosis of follicular thyroid cancer is not possible and this fact highlights the necessity for surgical treatment of any suspicious thyroid nodule. Aggressiveness of this tumor is greater than in the case of papillary thyroid cancer and it is the reason for radical surgical treatment of follicular thyroid cancer. Total thyroidectomy facilitates later adjuvant therapy with thyroid hormones and radioiodine. This procedure improves the outcome and the risk of relapse. Results of our study clearly demonstrate that diagnosis of follicular thyroid cancer in us is established in the early phase of the disease (78.57%), but the significant number of the patients (21.43%) is still in the advanced phase of the disease.
Rho-ROCK Expression Predicts the Prognosis in Patients with T3/T4 Gastric Cancer

A small GTPase Rho protein and an effector ROCK have significant roles in cancer adhsion, metastasis, invasion, angiogenesis and cell mortality. We investigated the expressions of RhoA protein and ROCK-1 protein in 100 patients with macroscopically T3/T4 gastric cancer immunohistochemically. The expression of RhoA was detected in gastric cancer specimens from 39 patients and that of ROCK-1 in specimens from 30 patients. The clinicopathological characteristics of 21 tumors with co-expression of RhoA and ROCK-1 proteins (Rho/ROCK ON) were compared with those of the 79 remaining tumors (Rho/ROCK OFF). The percentage of lymph node metastasis positive cases in the Rho/ROCK ON group (81%) was higher than that in the Rho/ROCK OFF group (66%), but the difference was not significant (P = 0.183). However, the prognosis of the 21 patients with Rho/ROCK ON was significantly poorer than that of the 79 with Rho/ROCK OFF (P = 0.006). Our results indicate that the evaluation of the protein expression of RhoA and ROCK-1 is useful for predicting the prognosis in patients with T3/T4 gastric cancer.
Severe Disability After Stroke: Outcome After Inpatient Rehabilitation

Objective: To determine the functional outcome following acute rehabilitation of patients with severe and very severe stroke using the Functional Independence Mea sure (FIM). Background: Most patients with severe and very severe stroke are reported in the literature to have a poor functional outcome. However, there are few studies that specifically address severity and their conclusions are confounding. Methods: We retrospectively reviewed charts of 41 consecutive patients with the primary diag nosis of ischemic or hemorrhagic stroke admitted to an inpatient rehabilitation unit with a admission FIM score of <60. Outcome measures included discharge residence, length of stay, and FIM score. Results: Over 63 percent (26 patients) were discharged to home. Discharge mean FIM scores (61.24) were significantly improved over the admission mean FIM (34.12) for self-care, mobility, communication, and social cog nition. The FIM Efficiency score was 0.356/day (mean[FIMdis-FIMadm]/mean LOS) as compared with previous reports of FIM Efficiency of 0.97/day for all stroke. Con clusion: Patients with severe stroke can experience improvement during inpatient rehabilitation and be discharged to a home setting, although the rate of improvement is less than that of more moderate stroke.
La estimulación olfativa previene la apnea en los recién nacidos prematuros

prematuridad consiste en metilxantinas y doxapram, pero no es totalmente eficaz y suele presentar efectos secundarios indeseables. El presente estudio examina si la exposición a un olor que se sabe que modula la frecuencia respiratoria del recién nacido puede reducir la frecuencia de los episodios apneicos. MÉTODO: Catorce neonatos pretérmino, de 24-28 semanas de edad gestacional al nacer y con apnea recurrente pese al tratamiento con cafeína y doxapram, fueron expuestos a un olor agradable, difundido durante 24 h en la incubadora. La eficacia del tratamiento olfativo se evaluó comparando la frecuencia y la gravedad de las apneas observadas durante el día de la administración del olor con las del día anterior (inicial) y las del día posterior (control tras el tratamiento). La definición de apnea fue el cese completo de movimientos respiratorios > 20 s o de menor duración asociado con hipoxia o bradicardia. RESULTADOS: Se observó una disminución del 36% en las apneas de cualquier tipo, encontrada en 12/14 recién nacidos. Las apneas sin bradicardia disminuyeron (44%) durante el día de administración de olor, y esta disminución afectó a todos los recién nacidos. La frecuencia de la apnea con bradicardia moderada (frecuencia cardíaca, entre 70 y 90 lat/min) se mantuvo, mientras que la frecuencia de la apnea asociada con bradicardia intensa (frecuencia cardíaca < 70 lat/min) disminuyó claramente (45%), y afectó a todos los recién nacidos. No se observaron efectos secundarios. CONCLUSIÓN: La introducción de un olor agradable en la incubadora tiene valor terapéutico en el tratamiento de las apneas que no responden a cafeína y doxapram.
Cost effectiveness of oseltamivir for the treatment of influenza in adults, adolescents and children in Finland

Summary The objective of this study was to perform an economic assessment of the use of oseltamivir, compared with usual care, for the treatment of patients presenting with influenza-like illness in Finland. Three patient subpopulations were distinguished: (i) otherwise healthy adults; (ii) patients at risk; and (iii) children. The analyses were based on a decision analytic model populated with data specific for Finland and using first- and second-order Monte Carlo simulations. Probabilistic sensitivity analyses were performed to assess the impact of uncertainty regarding the most appropriate value for the variables and to derive cost-effectiveness acceptability curves in order to summarise the results. From a societal perspective, oseltamivir treatment was found to reduce costs in all groups. From a healthcare payer's perspective, improvements in outcomes were obtained at relatively modest incremental costs. The estimated incremental cost per day of normal activity gained was €27 in healthy adults, €8 in elderly and at-risk patients, and €14 in children.
Pharmacokinetics of ceftriaxone in buffalo calves (Bubalus bubalis) following intravenous and intramuscular administration

Summary Pharmacokinetics of ceftriaxone was studied in buffalo calves (Bubalus bubalis) after single intravenous and intramuscular administration of 10 mg/kg body weight. The drug concentrations in plasma samples were measured by high performance liquid chromatography with UV detection. Following intravenous administration, the drug was rapidly distributed (Cp o : 106.5 ± 9.64 µg/ml; t1/2α: 0.09 ± 0.01 h; Vdarea: 0.48 ± 0.05 L/kg) and eliminated (t1/2β: 1.27 ± 0.04 h) from the body with a clearance rate of 4.40 ± 0.44 ml/min.kg. Following intramuscular administration, the peak plasma concentration of the drug was 15.8 ± 2.4 µg/ml at 0.5 h and the drug was detected up to 12 h. The drug was rapidly absorbed from the site of injection (t1/2ka: 0.35 ± 0.01 h), widely distributed (Vdarea: 1.53 ± 0.2 L/kg) and slowly eliminated from the body (t1/2β: 4.38 ± 0.4 h; ClB: 4.01 ± 0.30 ml/min.kg). The bioavailability of ceftriaxone was 70.2 ± 2.0% following intramuscular injection. Intramuscular injection of ceftriaxone has favourable pharmacokinetics and moderate bioavailability in buffalo calves and can be used for susceptible infections in calves.
Time-dependent activity of Na+/H+ exchanger isoform 1 and homeostasis of intracellular pH in astrocytes exposed to CoCl2 treatment.

Hypoxia causes injury to the central nervous system during stroke and has significant effects on pH homeostasis. Na+/H+ exchanger isoform 1 (NHE1) is important in the mechanisms of hypoxia and intracellular pH (pHi) homeostasis. As a well-established hypoxia-mimetic agent, CoCl2 stabilizes and increases the expression of hypoxia inducible factor‑1α (HIF-1α), which regulates several genes involved in pH balance, including NHE1. However, it is not fully understood whether NHE1 is activated in astrocytes under CoCl2 treatment. In the current study, pHi and NHE activity were analyzed using the pHi‑sensitive dye BCECF‑AM. Using cariporide (an NHE1‑specific inhibitor) and EIPA (an NHE nonspecific inhibitor), the current study demonstrated that it was NHE1, not the other NHE isoforms, that was important in regulating pHi homeostasis in astrocytes during CoCl2 treatment. Additionally, the present study observed that, during the early period of CoCl2 treatment (the first 2 h), NHE1 activity and pHi dropped immediately, and NHE1 mRNA expression was reduced compared with control levels, whereas expression levels of the NHE1 protein had not yet changed. In the later period of CoCl2 treatment, NHE1 activity and pHi significantly increased compared with the control levels, as did the mRNA and protein expression levels of NHE1. Furthermore, the cell viability and injury of astrocytes was not changed during the initial 8 h of CoCl2 treatment; their deterioration was associated with the higher levels of pHi and NHE1 activity. The current study concluded that NHE1 activity and pHi homeostasis are regulated by CoCl2 treatment in a time-dependent manner in astrocytes, and may be responsible for the changes in cell viability and injury observed under hypoxia-mimetic conditions induced by CoCl2 treatment.
Subjective and Objective Assessment of Edema during Adjuvant Chemotherapy for Breast Cancer Using Taxane-Containing Regimens in a Randomized Controlled Trial: The National Surgical Adjuvant Study of Breast Cancer 02

Objective: To elucidate the time course of taxane-induced edema which may affect the patients’ quality of life (QOL). Patients and Methods: Our study included the first 300 Japanese patients assigned to 1 of 4 regimens using docetaxel (DTX) or paclitaxel (PTX) by 1:1:1:1 in a randomized controlled trial to evaluate the efficacy of adjuvant therapies for node-positive breast cancer. Patients’ QOL was prospectively assessed by the Functional Assessment of Cancer Therapy (FACT)-breast and -taxane (FACT-T) subscale. The scores of FACT items regarding edema and body weight were used as indicators of edema. Results: The scores for ‘anasarca’, ‘edema of the hands’ and ‘edema of the legs and feet’ of the FACT-T subscale worsened up to 1–2 months after chemotherapy, and body weights increased remarkably until cycle 8 in patients treated with DTX alone (75 mg/m2, 8 cycles, every 3 weeks). Edema-related symptoms and body weight were relatively stable in the other treatment groups. There were statistically significant differences in the scores of those items and in the changes of body weight both between the DTX-alone group and the other three groups combined, and between the groups using DTX and those using PTX. Conclusion: Many patients receiving DTX for >4 cycles suffered significantly from edema.
Neoadjuvant, Anthracycline-Free Chemotherapy with Carboplatin and Docetaxel in Triple-Negative, Early-Stage Breast Cancer: A Multicentric Analysis of Feasibility and Rates of Pathologic Complete Response

Background: Triple-negative breast cancer (TNBC) attracts a disproportionate share of intensive research because of its poor prognosis. Standard anthracycline- and taxane-based regimens still yield an unsatisfactorily low rate of pathologic complete response (pCR). The pCR rate is a recognized surrogate marker for good long-term survival. Methods: A multicentric, retrospective study was conducted including all patients not willing to undergo or not suitable for an anthracycline-based regimen. Six cycles of docetaxel 75 mg/m2 and carboplatin AUC 6 q3w were administered. The primary endpoint was pCR (ypT0/ypTis + ypN0) and near-pCR (≤5 mm residual disease). The secondary endpoint was feasibility (CTCAE version 4.03 criteria) and adherence to treatment. Results: Six cycles of carboplatin AUC 6 and docetaxel 75 mg/m2 resulted in a high pCR rate of 50% and a combined pCR/near-pCR rate of 70%. Grade 3 and 4 toxicities were rare events and 28 of 30 (93%) patients completed all 6 cycles. No toxicity-related treatment discontinuation and no febrile neutropenia were registered. Conclusion: This chemotherapy regimen provides a highly effective and feasible strategy for patients not willing to receive or not suitable for an anthracycline-based treatment (cardiac ejection fraction <65% or age >65 years). Combinations of platinum compounds with taxanes and anthracyclines may be also desirable in TNBC.
Native Vitamin D in Patients with Chronic Kidney Disease not Treated with Dialysis

Vitamin D metabolism is involved in the regulation of bone metabolism and calcium homeostasis. Vitamin D receptors are, however, detectable in several tissues and organs not directly involved in the regulation of mineral metabolism; furthermore, not only bone cells, but also other cell types can synthesize active vitamin D. Altogether, these findings have suggested that vitamin D may have other potential effects in addition to the commonly known effects on mineral metabolism. Vitamin D deficiency can induce bone disease development and represents an important risk factor for neoplastic, autoimmune and cardiovascular diseases. This review focuses on the results of the main randomized trials on vitamin D supplementation in the general population and in patients with chronic kidney disease.
The Effect of Repeated Botulinum Toxin A Therapy Combined with Intensive Rehabilitation on Lower Limb Spasticity in Post-Stroke Patients

Objectives: This study is a retrospective investigation of the effects of repetitive botulinum toxin A therapy (BoNT-A) and intensive rehabilitation (IR) on lower limb spasticity in post-stroke patients. Methods: Thirty-five post-stroke patients was included in this study and received BoNT-A for the first time. A 12-day inpatient protocol was with 4 cycles of the treatment protocol. The severity of spasticity, motor function and brace status were evaluated. Results: The modified Ashworth Scale (MAS) score of ankle dorsiflexors, range of motion, walking speed and balancing ability were significantly improved after cycle 1. The improvement of spasticity and motor function was persistent through cycles 2–4. One-third of brace users were able to discontinue the use of a brace. All of these brace users showed a forward gait pattern prior to therapy. Conclusions: Repeated BoNT-A combined with IR improved lower limb spasticity in post-stroke patients. Our results suggest that patients who show the forward gait pattern prior to therapy may be able to discontinue the use of their brace after therapy.
Focused Update of Sex Differences in Patient Reported Outcome Measures After Stroke

Women experience worse outcomes after stroke than men1 despite their lower age-adjusted incidence of stroke.2 Previous reviews of sex differences in select stroke outcomes, including activity limitations,3–5 participation restriction,4 poststroke depression (PSD),3 and health-related quality of life (HRQoL),3,4 demonstrated that women had worse outcomes than men across many of these measures. Women’s greater age and stroke severity, as well as poorer prestroke function, seem to contribute to the sex difference in outcomes, but data on other contributing factors are limited.4 Existing reviews included studies published >5 years ago, and given the rapid increase in the number of studies addressing sex differences in stroke outcomes, an updated review is warranted. Full details of our methods are provided in the online-only Data Supplement. A previous review included studies up to 2007,3 so we reviewed studies from 2007 onwards that examined sex differences in patient reported outcome measures (PROMs) at ≤12 months after stroke, including activity limitations, HRQoL, participation restriction, impaired cognition, and mood.6 Full results tables are shown in the online-only Data Supplement. ### Activity Limitations Of 1875 articles identified, 22 studies (3 population based) that were designed to examine sex differences (Results and Table I in the online-only Data Supplement) met criteria for inclusion. The most common instrument to assess activity limitations was the modified Rankin Scale, followed by the Barthel Index. In 8 studies including ischemic and hemorrhagic strokes, unadjusted estimates showed that women had more activity limitations than men through significantly lower odds of good outcome (odds ratio [OR] range: 0.44–0.61)7–9 or greater odds of poor outcome (OR range: 1.29–1.62). 10–14 In multivariable adjusted analyses, women had worse outcome than men with significantly lower odds of good outcome (OR range: 0.37–0.75) or …
IL10 GGC Haplotype Is Positively and HLA-DQA1*05-DQB1*02 Is Negatively Associated with Radiographic Progression in Undifferentiated Arthritis

Objective. In rheumatoid arthritis (RA), many genetic markers, such as the shared-epitope (SE) alleles, are described in association with radiographic progression, but limited data are available on undifferentiated arthritis (UA). We investigated whether single-nucleotide polymorphisms (SNP) and haplotypes in immune response genes and HLA class II alleles are associated with radiographic progression in patients with early UA. Methods. Progression of radiographic damage was determined in white Dutch patients with early UA after 2 years of followup. Severe progression was defined as an increase in Sharp/van der Heijde Score ≥ 5 points after 2 years of followup. The remainder was classified as mild. These SNP were genotyped by Taqman technology: tumor necrosis factor (TNF) −1031, −863, −857, −308, −238; lymphotoxin-α (LTA) +368, +252; interleukin 10 (IL10) −2849, −1082, −819; IL1A −889, IL1B −31, +3953; and IL1RN +2018. Carriage of SE alleles and HLA-DQA1*05-DQB1*02 haplotype was established. These markers were analyzed in relation to radiographic progression. Results. Forty-eight out of 151 patients with early UA had severe radiographic progression. Severe radiographic progression was associated with an increased carrier frequency of SE alleles (OR 5.12, 95% CI 2.0–13.1, p < 0.001) and IL10 GGC haplotype (OR 2.8, 95% CI 1.4–5.8, p = 0.003). Mild radiographic progression was associated with the HLA-DQA1*05-DQB1*02 haplotype (OR 0.3, 95% CI, 0.1–0.8, p = 0.013) and with allele TNF −308A (OR 0.4, 95% CI, 0.2–0.9, p = 0.02). Conclusion. The SE and the IL10 GGC haplotype are associated with severe progression of radiographic damage, in contrast to the DQA1*05-DQB1*02 haplotype and the TNF −308A allele, which are associated with mild radiographic progression in early UA.
Psychopharmacology of Addiction

Addiction is a primary, chronic, neurobiological disease, with genetic, psychosocial, and environmental factors influencing its development. Developments in the psychopharmacology of addiction is much slower than the other disciplines of psychiatry. For a long time, social and behavioral therapeutic approaches are the only choices for the treatment of addictive disorders. Disulfiram was the only pharmacological agent approved for addiction treatment until the end of 20th century. Pharmacological treatment options available for treatment have grown along with our understanding of the neurobiological mechanisms underlying the development and persistence of addiction. Several new medications like naltrexone, acamprosate, methadone and buprenoprhine have been approved for the treatment of alcohol and opioid use disorders ever since. Based on ever-increasing information about neurotransmitter and receptors, many studies have been performed concerning craving and relapse prevention in recent years. Besides many other pharmacological agents have been focus of new researches for treatment of different types of addiction. The aim of this article is to briefly review the literature on psychopharmacology of addictive disorders and recent developments in this area.
Application and Interpretation of High-Sensitivity Cardiac Troponin Assays in Patients With Acute Ischemic Stroke

Cerebrovascular and cardiovascular diseases are major causes of death and disability worldwide. Ischemic stroke is a frequent complication in cardiac disease and, vice versa, cardiac complications commonly cause early clinical worsening and death after stroke.1 Adverse cardiac events account for the second largest group of deaths during the acute phase after stroke and are important determinants of long-term survival.2 Because of the close association between stroke and cardiac disease, current AHA/ASA guidelines for the early management of patients with acute ischemic stroke recommend assessment of cardiac biomarkers (preferably cardiac troponin [cTn]) in all patients presenting with acute ischemic stroke.3 Although the guidelines point out the potential prognostic significance of cTn, there are currently no recommendations on how to interpret cTn levels in the setting of ischemic stroke. Practice guidelines for interpretation of cTn generally include patients with stroke; specific recommendations, however, are scarce.4 Interpretation of cTn elevation in patients primarily presenting with ischemic stroke is complex because other conditions apart from acute thrombotic coronary artery disease (CAD) may also lead to the finding of an elevated cTn.4–6 What is more, clinical complaints associated with acute coronary syndromes may be atypical or masked by neurological deficits. Although early invasive coronary revascularization and potent antithrombotic therapy are lifesaving in patients with myocardial infarction (MI), caution is warranted in the context of an acute ischemic cerebral lesion. Recently, high-sensitivity cTn assays were developed, which enable detection of small amounts of circulating cTn.7,8 However, the marked increase in sensitivity for myocardial injury is accompanied by a reduced specificity for diagnosis of acute CAD. Consequently, the above-mentioned practice guidelines for applying highly sensitive cTn assays refer to stroke as one of the multiple clinical conditions, in which cTn testing has created clinical uncertainty.4 In …