Miracle-dz/UniFAR-FTUs huggingface dataset:
A Phase I Study of the Farnesyltransferase Inhibitor Tipifarnib in a Week- on Week-Off Dose Schedule in Acute Myelogenous Leukemia.

Tipifarnib (R115777, Zarnestra) is a methylquinolone analogue that is a potent inhibitor of farnesylation. The initial phase I study in leukemia by Karp and Lancet (Blood, 2001) showed clinical responses in 10/34 evaluable patients with AML on a 21 day schedule, with 600 mg bid identified as the MTD. Preclinical work shows that farnesyltransferase remains inhibited for seven days after tipifarnib, suggesting an alternate week dosing schedule. We report the results of a tipifarnib phase I dose escalation trial in AML on a week on week off schedule. Dose levels were 400, 600, 800, 1200, 1400, and 1600 mg BID on a standard 3+3 design. Eligibility was defined as relapsed or refractory AML after one to three prior induction regimens. A total of 37 patients were accrued, with 32 evaluable for toxicity. Median age at treatment is 62 (range 33–77), with 15 F, 22 M. RESULTS: The MTD on this schedule was 1200 mg B.I. D. , with the major dose limiting toxicity determined by course one being creatinine elevation. At the 6 pts treated at the MTD there was one DLT (grade 3 creatinine), one grade 3 nausea (not a DLT), and grade 2 toxicities including liver enzyme abnormalities, nausea/vomiting, and rash. At dose level 1, metabolic acidosis and hepatic failure in a patient with progressive leukemia who had previous hepatic toxicity during chemotherapy was observed. Two patients treated at the MTD had a complete remission: a 69-yr old male who relapsed after 231 days, and a 66-yr old male who relapsed after 258 days, but who responded to re-treatment with tipifarnib and is disease-free 548 days (18 months) since enrolling in the study. At 1000mg BID dose, a 69-yr old woman with relapsed AML after autologous transplant had a CR after 2 cycles and went on receive a successful allogeneic transplant and is in remission 2yrs from her first cycle of tipifarnib. One patient with AML evolving out of CMMoL had disappearance of the AML blasts but persistence of the CMMoL after two cycles at the 800 mg bid level, and one patient at the 1400 dose had a platelet rise to 140 from a starting platelet count below 40 despite continued presence of blasts. Higher doses resulted in a higher incidence of dose limiting renal toxicity, fewer courses, and no complete remissions. Additional patients are accruing at the MTD to further understand the toxicities on this schedule. In AML patients, a two-fold increase in tipifarnib dosing can be tolerated on this dosing schedule with responses seen at the higher doses. A monotherapy phase 2 or tipifarnib combination study in AML using this schedule appears warranted.
Management of patients with substance use illnesses in psychiatric emergency departament Manejo do paciente com transtornos relacionados ao uso de substância psicoativa na emergência psiquiátrica

Objective: Substance use disorders are prevalent in the emergency departments of medical and psychiatric services, accounting for up to 28% of cases in medical emergency departments. However, emergency department professionals identify less than 50% of the cases of alcoholrelated problems. This article aims to provide evidence-based interventions for the specific treatment of patients who meet diagnostic criteria for substance use disorders and who present to emergency rooms during intoxication or withdrawal. Method: A literature review was performed on the Medline database, using the English descriptors “acute intoxication”, “withdrawal”, “alcohol”, “cocaine”, “cannabis”, “opioid”, “inhalant”, and “management”. Results and Conclusion: The management of patients with substance use disorders should include a comprehensive assessment (medical and psychiatric), treatment of diagnosed disorders (withdrawal, intoxication, and clinical features that characterize an emergency), awareness of the patient to start treatment if necessary, and referral.
Stress among Medical Students and Its Association with Substance Use and Academic Performance

Background. Chronic stress among medical students affects academic performance of students and leads to depression, substance use, and suicide. There is, however, a shortage of such research evidence in Ethiopia. Objective. We aimed to estimate the prevalence and severity of stress and its association with substance use and academic performance among medical students. Methods. A cross-sectional survey was conducted on a sample of 329 medical students at Jimma University. Data were collected using the General Health Questionnaire (GHQ-12), Medical Students Stress Questionnaire (MSSQ-20), and Drug Abuse Surveillance Test (DAST). Data were analyzed using SPSS version 20.0. Logistic regression analysis and Student’s -test were applied. Results. The mean age of the respondents was 23.02 (SD = 2.074) years. The current prevalence of stress was 52.4%. Academic related stressor domain was the main source of stress among 281 (88.6%) students. Stress was significantly associated with khat chewing [AOR = 3.03, 95% CI (1.17, 7.85)], smoking [AOR = 4.55, 95% CI (1.05, 19.77)], and alcohol intake [AOR = 1.93, 95% CI (1.03, 3.60)]. The prevalence of stress was high during the initial three years of study. Stress was significantly ( ) but negatively ( ) correlated with academic achievement. Conclusion. Stress was a significant problem among medical students and had a negative impact on their academic performance. Year of study, income, and substance use were associated with stress. Counseling and awareness creation are recommended.
The 1.7 Angstrom X-Ray Crystal Structure of the Porcine Factor VIII C2 Domain and Binding Analysis to Anti-Human C2 Domain Antibodies and Phospholipid Surfaces

The factor VIII C2 domain is essential for binding to activated platelet surfaces as well as the cofactor activity of factor VIII in blood coagulation. Inhibitory antibodies against the C2 domain commonly develop following factor VIII replacement therapy for hemophilia A patients, or they may spontaneously arise in cases of acquired hemophilia. Porcine factor VIII is an effective therapeutic for hemophilia patients with inhibitor due to its low cross-reactivity, however, the molecular basis for this behavior is poorly understood. In this study, the X-ray crystal structure of the porcine factor VIII C2 domain was determined, and superposition of the human and porcine C2 domains demonstrates that most surface-exposed differences cluster on the face harboring the “non-classical” antibody epitopes. Furthermore, antibody-binding results illustrate that the “classical” 3E6 antibody can bind both the human and porcine C2 domains, although the inhibitory titer to human factor VIII is 41 BU/mg IgG versus 0.8 BU/mg IgG to porcine factor VIII, while the non-classical G99 antibody does not bind to the porcine C2 domain nor inhibit porcine factor VIII activity. Lastly, differences between the electrostatic surface potentials suggest that the C2 domain binds to the negatively charged phospholipid surfaces of activated platelets primarily through the 3E6 epitope region. In contrast, the G99 face, which contains residue 2227, should be distal to the membrane surface. Phospholipid binding assays indicate that both porcine and human factor VIII C2 domains bind with similar affinities, and the human K2227E mutant binds to phospholipid surfaces with a modestly decreased affinity. Disclosures No relevant conflicts of interest to declare.
Immunosuppressive Effects of Multipotent Mesenchymal Stromal Cells on Graft-Versus-Host Disease in Rats Following Allogeneic Bone Marrow Transplantation.

The major obstacle to successful bone marrow transplantation (BMT) is graft versus host disease (GVHD). Multipotent mesenchymal stromal cells (MSC) have shown immunosupressive effects. The aim of this study was to investigate the effect of MSC on the prevention of GVHD in a rat BMT model. We prepared rat GVHD model using allogeneic BMT+4x108 donor splenocyte infusion (DSI). Allogeneic BMT were performed from Spraque Dawley (SD) rats to female Wistar rats by applying 1x108 mononucleer cells (MNC) via tail vein. The recipient animals were conditioned with a myeloablative regimen consisted of 950 cGy total body irradiation prior to BMT. GVHD prophylactic regimen was performed 3 mg/kg/day cyclosporine-A (CsA)+0.25 mg/kg methotrexate (Mtx) IP +1. , +3. , +6. days. The rats were divided into three control group (CG) and four study group (SG) (n=7). CG-I; only allogeneic BMT+DSI (GVHD model), CG-II; only myeloablative regimen, CG-III; only inspection. GVHD model was performed in all SGs and then SG-I receiving only GVHD prophylactic regimen, SG-II receiving only MSC, SG-III receiving GVHD prophylactic regimen+MSC, SG-IV receiving MSC after GVHD findings developed. Gross (diarrhea, lose weighting, skin findings), histopathological, and immunophenotypical (CD4, CD8, CD25 and plasma IL-2 levels) examinations of GVHD following allogeneic BMT, and the survival analysis of all groups were performed. The survival following allogeneic BMT was significant longer (p
Prescribing of potentially inappropriate psychotropic medications for older, community-dwelling adults

Antidepressants, sedatives and antipsychotics are used to treat various behavioral, psychiatric and neurological disorders. However, the risk of adverse events challenges prescribing for older adults. The use of most antidepressants, all sedatives in older adults and the use of antipsychotics in elderly with dementia are considered “potentially inappropriate” by Beers 2012 criteria. This study aims to: (i) describe the prevalence of potentially inappropriate psychotropic (antidepressant, sedative, antipsychotic) prescribing for older community-dwelling Americans; (ii) assess the influence of sociological factors on potentially inappropriate psychotropic choices; and (iii) assess the relationship between potentially inappropriate psychotropic choices and emergency outcomes. Visits by older adults (>65 years) to office-based physicians across the US were extracted from the National Ambulatory Medical Care Survey 2010. Orders for antidepressants, sedatives and antipsychotics were classified based on Beers criteria. Multivariate logistic regression models were used to assess the influence of the various determinants on the choice of antidepressants, sedatives and the use of antipsychotics in dementia. Bivariate logistic regressions measured the risk of emergency referrals or hospitalizations following the visit. Although office-based physicians in the US rarely prescribe potentially inappropriate psychotropic medications to be avoided in older adults, many patients are exposed to classes that should be avoided in selected conditions due to drug-disease interactions. The use of electronic medical records is significantly associated with improved quality of antidepressant and sedative prescribing, through selection of more appropriate choices. Patient age, race, asthma, hypertension, obesity, and practice ownership are also associated with improved quality of psychotropic prescribing. Conversely, depression, income, and specialty are associated with higher risks of inappropriate psychotropic choices. Although increased consultation time was associated with less inappropriate antidepressant prescribing, this was reversed for antipsychotic prescribing in dementia. Patients receiving tertiary tricyclic antidepressants and patients with dementia receiving antipsychotics are at risk of emergency referrals or hospitalization. The determinants identified by this study may be used to develop quality indicators, and interventions to improve the quality of prescribing of antidepressants, sedatives and antipsychotics for older adults. INDEX WORDS: psychotropic, antidepressants, sedatives, anxiolytics, antipsychotics, older adults, community, inappropriate, prescribing quality PRESCRIBING OF POTENTIALLY INAPPROPRIATE PSYCHOTROPIC MEDICATIONS FOR OLDER, COMMUNITY-DWELLING ADULTS
EFFECT OF DIFFERENT LOW BACK TRAINING PROGRAMS ON LUMBAR SPINE KINESTHESIA

Reduced kinesthetic perceptions can impair lower back sensorimotor functions and result in increased injury risk. The effect of low back training programs on lumbar spine kinesthetic sensibility is undetermined. There was a back strengthening exercise group (with low back pain; training 4.4 h/wk), a “classical” back training program group (with low back pain; training 4.9 h/wk) and a control group (training 5.4 h/wk). During an active reproduction test, subjects performed trunk positions in random order: flexion [A(0°-20°), B(20°-40°)], lateral flexion [C(0°-30°)], Using a 3D-ultrasound motion analysis system the repositioning error was calculated from the given target position to the subject perceived target position, before and after a 5 week training period. Results show decreased repositioning error after the training for both training groups.
Papel de la resonancia magnética en la decisión del tratamiento quirúrgico en pacientes con diagnóstico reciente de cáncer de mama

Objective: determine the implications, in surgical management of patients with recent diagnosis of breast cancer, of preoperative magnetic resonance studies. Patients and methods: retrospective, transverse analysis of magnetic resonance breast studies (n = 200) performed by the Hospital San Jose TEC de Monterrey Radiology and Imaging Department, from May 2010 through June 2013. One hundred and one patients with recent diagnosis of breast cancer confirmed histologically and with conventional image studies (mammogram and ultrasound), in addition to magnetic resonance, were included. An observer retrospectively analyzed the image studies (mammogram, ultrasound) to determine unifocal, multifocal, multicentric disease (using the BIRADS system), to evaluate the extent of the disease and to distinguish the therapeutic approach (conservative surgery vs. mastectomy) proposed initially. In the second stage, all magnetic resonance studies (Magnetom 1.5T, Siemens® Medical System) performed on the same patients were analyzed to evaluate the local extent of the cancer and check for additional foci which could change the approach in surgical treatment. The incidence of additional cancerous lesions detected by magnetic resonance and not suspected in conventional image studies was determined; finally, the percentage of change in surgical treatment from the initial proposal was calculated. Results: In 68/101 patients conservative surgery was considered the appropriate treatment. Following review by magnetic resonance of breasts, a therapeutic change was considered in 43 patients (42.57%); more extensive surgery (quadrantectomy instead of tumorectomy) was recommended in 9 cases (8.9%) due to additional cancerous lesions (multifocal disease); in 30 cases (29.7%) mastectomy instead of conservative surgery (23 cases were due to detection of additional cancerous lesions in relation to multicentric disease, in 7 cases due to greater extension of the primary tumor). In 4 cases (3.9%) tumorectomy was indicated due to detection of synchronous cancer in the contralateral breast. Conclusion: magnetic resonance of breasts often helps to discover additional malignant lesions not detected by conventional imaging methods; this leads to changes in surgical approach, usually to more extensive surgeries.
Evalution of front line demonstration trials on barley in Dausa district of Rajasthan

The study was undertaken to investigate the impact of front line demonstration on Barley. A total of 134 demonstrations having the similar number of traditional practices or local check were conducted in 70 ha area in eleven different village in Dausa district of Rajasthan Yield of front line demonstration trials and potential yield of the respective variety and year were compared to estimate the yield gap which were further categorized into technology and extension gaps. Technology gap was found highest (1530) in case of Rd-2552 at village Dubbi in 2009–10 and lowest (330) of RD-2660 at village Reta in the year 2008–09. Technology index shows the feasibility of the evaluated technology on the farmers’ fields’. The lower the value of the technology index more feasibility of technology. Technology index was highest i.e. 44.61 per cent at village Dubbi in the year 2009–10, and lowest 7.06 per cent at village Reta in 2008-9. The study indicated that average per cent increase in grain yield was 15.05 (558 kg/ha) and straw yield 11.15 (504 Kg/ha). On the basis of present status of area of Barley in Dausa district (6825) farmer can get 3640 metric tons additional production which is essential fulfillment demand and supply gap. On the basis of net returns (Rs/ha) of various front line demonstrations on Barley in different years, the highest percent increase were found 30.94 per cent at village Bhadoli in year 20056 with the variety of RD-2552 followed by 28.58 per cent at village Lawan in year 2008-9 with the variety RD-2552. Across the years front line demonstrations were found higher productivity ranging from 4.93 to 20.92 per cent and higher B: C ratio from 2.24 to 2.84. Front line demonstrations shows in respect of per cent increase of yield and B:C ratio is sufficient for increasing production of Barley and increasing living standard of farmers community of Dausa district. The study reveals that overall per cent increase in net returns was 21.72(Rs 5250/ha).
SP834RISK FACTORS AND THEIR RELATIVE STRENGTHS FOR NEW ONSET DIABETES AFTER TRANSPLANTATION (NODAT)

Introduction and Aims: To determine the risk factors for new-onset diabetes after transplantation (NODAT) Methods: This is a retrospective observational cohort study. All adult patients transplanted over a 9 year period were included provided that they had no evidence of pre-transplant diabetes and had a functioning graft for ≥12 months. Data collected include age, sex, family history (FH) of diabetes, BMI and type of donor source. The pre-transplant fasting blood sugar (FBS) levels, at and during the first 24 hours post transplantation, at 6 months and 12 months post-transplant were measured. Results: There were 279 patients in the study with a mean age of 36.3±13.2 years, mean BMI of 26.5±7.2 and mean pre-transplant FBS of 5.0±0.8 mmol/l, which rose to 9.6± 4.8 mmol/l after 24 hours with the highest level during the first 24 hours being 14.1-±8.3 mmol/l. Fifty-seven patients (20.4%) developed NODAT. This group was significantly older (43.6±10.7 versus 34.2±13.1 years respectively; p=0.000), heavier (78.8±13.7 versus 66.9 ±19.2 kgs respectively; p=0.000), with higher BMI (30.6±5.0 versus 25.8±7.0 respectively; p=0.000) than the group that did not. They also had a higher FBS level after 24 hours of transplantation (10.9±4.1 versus 9.4±4.9 mmol/l respectively; p=0.03), at 6 months (7.9±3.7 versus 5.3±1.0 mmol/l respectively; p=0.000) and at 12 months (9.0±3.8 versus 5.3±1.0 mmol/l respectively; p=0.000) (table 2). No significant differences were observed between the two groups in height, FBS in the pre transplant workup or serum creatinine levels at 6 or 12 months. The incidence of NODAT was not affected by gender (13% in males and 18.5% in females (p=0.2) or by kidney donor type (15.8% for LD and 15.0% for DD (p=0.9). However, it was significantly higher in those with a FH of DM than to those without (37.2 % and 1.2 % respectively (P=0.000 (RR 31.3; 95% CI 7.7-126) In the group with NODAT, 18.0% had a FBS at 24 hours >6 (mmol/l) but only 4% with FBS at 24 hours 35 year but only 8.8 % were aged 26.1 but only 5.9 % had a BMI of < 26.1 (p=0.000) (RR 1.26 95% CI 1.136 to 1.406) and 37.7 % had a FH of DM but only 1.2 % had no FH of DM (p=0.000) (RR 31.3 95% CI 7.730 to 126.812) The risk was not altered by gender (p=0.2 RR 1.07 (95% CI 0.96-1.18) or transplant donor type (P=1.0 RR 1.05 (95% CI 0.597-1.84) Multivariate analysis confirmed FH of DM, age and FBS level at 24 hours as independent risk factors Conclusions: A fifth of the patients developed NODAT with the risk factors being older age, higher BMI, higher FBS 24 hours after transplantation and family history of DM.
PROMISING PHARMACEUTICAL APPLICATIONS OF HONEY: A REVIEW

Medicinal uses of honey have been archived in the world's medical literature, and since olden times, it has been known to possess many useful properties. Honey has been used in traditional medicines, alone or in conjunction with other substances, and has been administered both topically and orally. In addition, natural honey has been subjected to clinical and a laboratory examination by several expert groups and it has managed to find a position in modern medicine. Inhibitory effect of honey has been reported on over 60 species of bacteria, viruses and a few species of fungi. Antioxidant activity of honey is attributed to a wide range of compounds including peptides, phenolics, organic acids, enzymes, and glucose oxidase that contains gluconic acid and hydrogen peroxide which are important in treatment of many disease conditions. Honey has been successfully used in hemodialysis, diabetic foot ulcers (DFUs), autolytic debridement, mucositis, vernal keratoconjunctivitis and hemorrhoid. This review covers ancient mythology, composition, morphological properties and the most salient uses of honey in modern human diseases which are supported by recent clinical trials cited in medical journals.