Miracle-dz/UniFAR-FTUs huggingface dataset:
Latino Immigrants Describe Residence in Rural Midwestern Meatpacking Communities: A Longitudinal Assessment of Social and Economic Change

The authors describe results from a longitudinal investigation of Latino immigrants residing in three rural, Midwestern, meatpacking communities. Qualitative and quantitative data were collected from 43 Latino immigrants. Survey data assessed economic strain, community concerns, and community service access and availability; in-depth interviews focused on satisfaction with rural Midwestern residence. The following year, 23 of the original participants were located. They completed the same instruments and engaged in an in-depth interview to assess change during the previous year. Results of this investigation are presented as are suggestions for further work and advocacy efforts.
Vaccines as early therapeutic interventions for cancer therapy: neutralising the immunosuppressive tumour environment and increasing T cell avidity may lead to improved responses

Importance of the field: Considerable progress has been made in identifying the antigens recognised by the immune system. This has led to the success of monoclonal antibody therapy and the recent approval of prophylactic vaccines that give excellent protection against cervical cancer. Provenge will shortly be the first therapeutic vaccine to be approved. Areas covered in this review: Our aim is to discuss the recent success with prophylactic cancer vaccines for prevention of cancer and the progress with therapeutic vaccines design to eradicate established tumours. Therapeutic vaccines need to stimulate high-avidity T cell responses that can recognise and kill tumours. How this can be achieved in cancer patients is discussed. The immunosuppressive tumour environment also needs to be modified to allow extravasation and efficacy of the vaccine induced T cells. What the reader will gain: An insight into the limitations of present cancer vaccine approaches and how they can be manipulated to give more effective anti-tumour responses. Take home message: A combination of more effective vaccines that stimulate high-avidity T cells, in combination with drugs or monoclonal antibodies that neutralize immunosuppressive factors within the tumour environment are needed to improve the efficacy of immunotherapy of cancer.
Peg-asparaginase for acute lymphoblastic leukemia

Importance of the field: Asparaginase is a prominent component of pediatric and adolescent treatment for acute lymphoblastic leukemia. These treatment regimens are now being employed in adults. Knowledge of the efficacy and toxicity of asparaginase preparations is essential when using these treatments. Areas covered by this review: The search terms used were asparaginase, leukemia, pegylated, oncaspar, adolescent and young adult. Literature was searched in Pubmed/Medline with no limitations on year of publication. Abstracts from the American Society of Hematology meetings and the American Society of Clinical Oncology were searched from 2004 – 2008 using the same terms. What the reader will gain: The reader will gain knowledge of the tolerability and efficacy of pegylated asparaginase when treating acute lymphoblastic leukemia. Take home message: Pegylated asparaginase is generally well tolerated in adult patients with efficacy that appears to be at least equivalent to native asparaginase preparations.
Déficit nutricional em crianças de uma cidade de grande porte do interior da Bahia, Brasil

The study sought to analyze the nutritional deficit of children and associated environmental factors and maternal and infant characteristics in a major city in the interior of the state of Bahia. Information from mother/child-under-four duos of a birth cohort was assessed. Malnutrition was defined by the height-for-age (H/A) anthropometric index, at a cutoff of -1 z-score relative to the benchmark of the 2006 Multicentre Growth Reference Study. The variables studied were: the characteristics of children (birth weight and multiple births) and mothers (age at the time of birth, education level, parity and performing prenatal exams) and environmental factors (floor and roof material of residence, source of water consumed, indoor plumbing, water used for consumption and ownership of a refrigerator). Logistic regression was used to identify factors associated with nutritional deficit. Nutritional deficit occurred in 24.6% of children. Underweight at birth, inadequate prenatal care, precarious nature of the floor of the home and no indoor plumbing were predictors of malnutrition among children in the study. Factors associated with malnutrition confirm the contribution of social issues in the genesis of malnutrition.
GM-CSF pathway correction in pulmonary alveolar proteinosis

Importance of the field: Pulmonary alveolar proteinosis (PAP) is a rare disease in which the abnormalities in surfactant metabolism are caused most often by impairments of GM-CSF pathway at different levels in different disease subsets (congenital, secondary, acquired/idiopathic) and for which there are only few, costly invasive therapeutic methods. Areas covered in this review: This review discusses these impairments, and their pathogenic and clinical consequences along with potential corrective therapies such as exogenous inhaled GM-CSF. What the reader will gain: Among the PAP disease subsets, in autoimmune PAP the GM-CSF autoantibodies play a major role in disease pathogenesis and their deleterious pulmonary effects can be blocked efficaciously with inhaled GM-CSF. Take home message: In PAP correction of the abnormalities of the GM-CSF pathway represent a plausible approach demonstrated to be efficacious also in the case of inhaled GM-CSF used for autoimmune PAP.
Adalimumab in ulcerative colitis: hypes and hopes

Importance of the field: The advent of anti-TNF-α monoclonal antibodies has dramatically changed the management of inflammatory bowel diseases (IBD). Unlike Crohn's disease (CD), only one anti-TNF-α agent, infliximab, is currently approved for active moderate-to-severe ulcerative colitis (UC). Adalimumab is a fully human anti-TNF-α antibody that is effective and safe for the treatment of luminal and fistulising CD. Areas covered in this review: This review of the literature summarizes available data on of efficacy and safety profile adalimumab in patients with UC. What the reader will gain: Adalimumab may be effective in inducing and maintaining clinical remission in patients with moderate-to-severe UC. It may also induce mucosal healing and reduce the need for colectomy in patients with severe disease. The safety profile of the drug in UC is consistent with previous experience with this drug in CD. Take home message: Adalimumab may be effective and well tolerated in UC. Its efficacy in maintaining clinical remission needs to be confirmed in a randomized controlled trial.
Protective effect of peroxisome proliferator activator receptor (PPAR)-α and -γ ligands against methotrexate-induced nephrotoxicity

Abstract Context: The anticancer drug methotrexate (MTX) may cause multi-organ toxicities, including nephrotoxicity. Objective: To investigate effects of peroxisome proliferator activator receptor (PPAR)-α and -γ agonists; fenofibrate (FEN) and pioglitazone (PIO), in MTX-induced nephrotoxicity in rats. Methods: Rats were given FEN or PIO (150 or 5 mg/kg/day, respectively) orally for 15 days. MTX was injected as a single dose of 20 mg/kg, i.p. at day 11 of experiment, with or without either PPAR agonists. Results: MTX induced renal toxicity, assessed by increase in serum urea and creatinine as well as histopathological alterations. MTX caused renal oxidative/nitrosative stress, indicated by decrease in GSH and catalase with increase in malondialdehyde and nitric oxide (NOx) levels. In addition, MTX increased renal level of the pro-inflammatory cytokine; tumor necrosis factor (TNF)-α and up-regulated the expression of both the inflammatory and apoptotic markers; NF-κB and caspase 3. Pre-administration of FEN or PIO to MTX-treated rats improved renal function and reversed oxidative/nitrosative parameters. Interestingly, pre-administration of PIO, but not FEN, decreased renal TNF-α level and NF-κB expression compared to MTX alone. Furthermore, PIO had more significant effect than FEN on reversing MTX-induced renal caspase 3 expression. Discussion: Both FEN and PIO conferred protection against MTX-induced nephrotoxicity through comparable amelioration of oxidative/nitrosative stress. FEN lacked any effect on TNF-α/NF-κB, which was reflected on its less improvement on renal histopathology and apoptosis. Conclusion: At indicated dosage, PPAR-γ ligand; PIO shows better improvement of MTX-induced nephrotoxicity compared to PPAR-α ligand; FEN due to differential effect on TNF-α/NF-κB inflammatory pathway.
Ultra-high dose methylcobalamin (E0302) prolongs survival of ALS: Report of 7 years’ randomised double-blind, phase 3 clinical trial (ClinicalTrials.gov NCT00444613) (P7.060)

OBJECTIVE: To investigate the efficacy and safety of ultra-high dose (25mg or 50mg i.m. twice weekly) of methylcobalamin compared with placebo for amyotrophic lateral sclerosis (ALS) patients. BACKGROUD: High-dose methylcobalamin showed neuroprotective effects in acrylamide neuropathy (Watanabe et al.1994) and the increase in compound muscle action potential in a trial for ALS (Kaji et al.1998). DESIGN/METHODS: Patients (373) who were diagnosed with definite, probable, or probable-laboratory-supported ALS by revised El Escorial criteria were enrolled in this study. Those with [percnt]FVC less than 60[percnt] and the disease duration more than 3 years were excluded. Patients were randomly assigned to receive placebo, 25mg, or 50mg methylcobalamin i.m. twice weekly for 182weeks. Primary endpoints were event-free survival (time until death, TIPPV or all-day NIPPV) and ALS Functional Rating Scale-Revised (ALSFRS-R) changes. RESULTS: Of 373 patients, 370 (placebo 123, 25mg 124, 50mg 123) constituted the full analysis set. In both endpoints, there was no statistical significance in the comparison for the two dose response contrasts (linear and saturate hypothesis). For the patients who were given diagnosis of ALS within 12months after the onset (placebo 48, 25mg 54, 50mg 42), the event-free survival was prolonged in a dose-dependent manner (P=0.010, hazard ratio [95[percnt]CI] vs 25mg, 50mg were 0.640 [0.377, 1.085], 0.498 [0.267, 0.929], respectively) and ALSFRS-R changes were smaller in active groups (P=0.003) than in placebo. No adverse events of particular concern were noted. DISCUSSION: The diagnosis of ALS with revised El Escorial criteria is often delayed but newly-devised Awaji criteria have enabled earlier diagnosis. Patients are less likely to benefit from ultra-high dose methylcobalamin treatment if more than 2 to 3 years have passed since the onset of ALS. CONCLUSION: The present study demonstrated for the first time that ultra-high dose methylcobalamin can significantly prolong survival and retard progression in ALS if administered early. Disclosure: Dr. Kaji has received research support from GlaxoSmithKline and Eisai Inc. Dr. Kuzuhara has nothing to disclose. Dr. Iwasaki has nothing to disclose. Dr. Okamoto has nothing to disclose. Dr. Nakagawa has nothing to disclose. Dr. Imai has nothing to disclose. Dr. Takase has nothing to disclose. Dr. Shimizu has nothing to disclose. Dr. Tashiro has nothing to disclose.
Focus on skin cancer association and progression under TNF antagonist therapy

Introduction: Basal and squamous cell carcinomas are the most common non-melanoma skin cancers (NMSC) in humans. Their prevalence is higher in immunocompromized patients. Results of some animal experiments have indicated that TNF acts both as a tumour promotor and an inductor of apoptosis. Areas covered: Peer-reviewed articles about human skin cancers possibly related to TNF antagonists. The occurrence and growth kinetics of NMSC are possibly increased in some patients under TNF antagonist therapy. Other issues of such biological treatment suggested include the activation of other distinct skin malignancies, including malignant melanoma. Benign melanocytic tumours appear to be boosted as well. At present, most of the reported findings only represent anecdotal case reports. The influence of cumulative co-factors must not be neglected, particularly the effect of other therapies administered to the patients. The occurrence of antibodies to some TNF antagonists may decrease both the treatment efficacy and the risk of skin cancer progression. Expert opinion: More research needs to be performed in order to firmly establish and understand the risk of anti-TNF biologicals in the area of human skin cancers. At present, NMSC progression appears to be boosted on areas of skin field cancerization. Benign melanocytic naevi may develop as well.
Survival analysis of patients with bladder cancer, life table approach

Background: Bladder cancer is the fourth most common malignancy in men and the eighth most common in women. It causes 8% of all malignancies in men and 3% of all malignancies in women. The trend of bladder cancer is increasing in Iran. This study was conducted to estimate the survival rate of bladder cancer based on life table method. Materials and Methods: In this study, at first, data were collected based on individual variables of 514 patients suffering from bladder cancer and referred them to cancer registry center of Shiraz University of Medical Sciences from 2001-2009. Data were collected at two stages and analyzed by life table method and Wilcox on test. Significant level considered at 0.05. Results: Our findings showed that probability of survival accumulation at the end of 1, 3, 5, 10 years in patients with bladder cancer were equal to 0.8989, 0.7132, 0.5752 and 0.2459 respectively. There was significant difference in survival rate among age groups and treatment types (P < 0.05). However, we did not observe any difference in survival time based on smoking (P = 0.578), alcohol (P = 0.419) and education level (P = 0.371) of patients. Conclusion: The overall survival rate of bladder cancer in the present study was less than other areas. Patients’ age and treatment type were the influential factor in survival time. So continuous screening for early diagnosis suggested for older people.
Effect of mifepristone (25 mg) in treatment of uterine myoma in perimenopausal woman

Objectives: To evaluate the effect of Mifepristone (25 mg) on symptomatic myoma in perimenopausal women. Study Design: Open label clinical trial. Materials and Methods: Ninety three perimenopausal women of age 35-50 years having symptomatic myoma were selected from Gynecology OPD and given 25 mg Mifepristone once daily continuously for three months. Variables as; baseline uterine size, uterine volume, myoma size, volume, their number, position, characteristics, hemoglobin and blood parameters, were taken and followed monthly for six months. Bleeding and pain scores were checked on monthly visits. Changes in above parameters were tabulated during the first three months treatment phase and then next three post-treatment phase for analysis. Statistical Analysis: Was done by calculating mean, standard deviation, standard error and percentage distribution of variables. Results: Menorrhagia was the most common symptom which led patients to report to hospital. Mean uterine volume reduced to 63.69% of baseline, Mean dominant Myoma volume reduced to 53.62% and hemoglobin level raised to 137% after complete three months of treatment. Changes persisted in next three months post-treatment follow-up, while hysterectomy was required in 10 (12.2%) cases. Conclusion: Three months treatment of 25 mg Mifepristone effectively controls bleeding, reduces the uterine and myoma volume and thus can avoid blood transfusion and hysterectomy in a lot of symptomatic myoma cases.
Autologous bone marrow cell therapy for patients with peripheral arterial disease: a meta-analysis of randomized controlled trials

Objective: Early-phase clinical trials suggest that autologous bone-marrow-derived cells (BMCs) may have a positive effect on patients with severe peripheral arterial disease (PAD). However, the therapeutic effects of BMCs treatment in various aspects remain controversial. Research design and methods: We conducted a meta-analysis using data from randomized controlled trials (RCTs) by comparing autologous BMCs therapy with controls in patients with severe PAD. Pubmed, EMBASE, EBSCO and the Cochrane Central Register of Controlled Trials ( to approximately April 2011) were searched. Results: Seven RCTs with 276 patients were included. Pooled comparisons of studies found that BMCs therapy significantly improved ankle-brachial index (ABI) by 0.10 (95% CI, 0.07 to 0.14; p < 0.00001), transcutaneous oxygen tension (TcO2) by 13.39 mmHg (95% CI, 6.69 to 20.1 mmHg; p < 0.0001) and pain-free walking distance by 119.91 m (95% CI, 90.71 to 149.11 m; p < 0.00001). BMCs therapy significantly decreased scale of rest pain by 1.13 (95% CI, -1.71 to -0.54, p = 0.0002) and helped heal ulcers (OR, 7.17; 95% CI, 2.66 to 19.32; p < 0.0001). Conclusions: Our analysis based on seven RCTs suggests that autologous BMCs therapy, has a beneficial effect on physiologic and anatomic parameters in patients with severe PAD.
A review on the use of hyaluronic acid in tympanic membrane wound healing

Introduction: Tympanic membrane perforation represents a significant morbidity, especially if it occurs during a child's speech and language development. Recently, there has been an increased interest in hyaluronic-acid-related research and products as a potential therapeutic option for tympanic membrane perforation repair. Areas covered: This review describes the physical and chemical properties of hyaluronic acid and examines the role of hyaluronic acid in wound healing, in particular on the tympanic membrane. It also reviews the safety and efficacy of hyaluronic acid and its derivatives in animal studies as well as in clinical trials. Finally, it considers the potential future clinical applications in tympanic membrane perforation repair. Expert opinion: Hyaluronic acid has been found to accelerate tympanic membrane perforation closure, shorten the period of healing, produce a better quality neo-membrane and improve hearing. More importantly, hyaluronic acid is biodegradable, safe and biocompatible in the ear. Recently, there has been a trend towards the use of modified hyaluronic acid. However, there is a lack of higher-level evidence to support the use of hyaluronic acid in tympanic membrane perforations in the clinical setting. More large-scale randomised control trials are warranted before these bio-devices will be used routinely.
Obinutuzumab for the treatment of lymphoproliferative disorders

Introduction: Targeted therapy against CD20 with the mAb rituximab has led to significant improvements in survival for patients with B-cell non-Hodgkin's lymphoma (NHL). Despite these improvements, many patients relapse and/or become refractory after rituximab-containing therapies and thus better therapies are required for NHL. Areas covered: Obinutuzumab is a novel, humanized, anti-CD20 mAb currently being investigated in Phase III studies in comparison to rituximab. An overview of obinutuzumab, its mechanisms of action and the results of pre-clinical and Phase I/II studies are presented. Expert opinion: Pre-clinical studies suggest that obinutuzumab is a more potent anti-CD20 mAb than Rituximab at inducing antibody-dependent cellular cytotoxicity (ADCC) and direct cell death (DCD). Obinutuzumab is safe and effective in CD20 + NHL and further study is warranted. Results of ongoing Phase III clinical trials comparing Obinutuzumab to Rituximab in different disease settings and with different chemotherapy regimens are eagerly awaited.
Integrins and Monocyte Migration to the Ischemic Myocardium

ABSTRACT Aims: Characterize mononuclear cell migration after acute-myocardial infarction (MI). Material and Methods: Male Lewis rats underwent a left thoracotomy and ligation of the left anterior descending coronary artery (MI group). Control animals underwent thoracotomy without ligation (Sham group). Animals were sacrificed at 0, 2, 4, or 24 hr after the onset of ischemia. Leukocyte migration was assessed using isolated and In111 labeled mononuclear cells (injected at the onset of ischemia) and γ-count determined at 24 hours. Inhibition of migration was evaluated with monoclonal anti α4 and/or β2 antibodies. Results: Serum troponin was significantly elevated in animals with MI as compared with Sham (p = .017). Labeled mononuclear cell migration was five-fold higher in MI-treated animals than in Sham (p = .006). ED-1 positive mononuclear cells were confirmed in the left myocardium after 24 hr of ischemia. MCP-1 mRNA was significantly elevated in the left myocardium at 2 hr and 4 hr and peaked at 24 hr (p <.05). In addition, α4 integrin blockade inhibited labeled mononuclear cell migration by 22%. Blockade of β2 integrin inhibited mononuclear cell migration by 48%, while the combined α4+β2 blockade resulted in 59% inhibition of labeled mononuclear cell migration compared with treatment with isotype control antibody (p = .001). Conclusions: Significant ED1+ mononuclear cell migration within 24 hr of MI correlated with peak MCP-1 mRNA. Monoclonal antibody blockade suggested that early mononuclear cell migration is dependent only in part on α4 and β2 integrins.
Chemokine-dependent B cell–T cell interactions in chronic lymphocytic leukemia and multiple myeloma – targets for therapeutic intervention?

Introduction: Chemokines and their receptors play essential roles in the development, maintenance and proper functioning of the immune system. B cell–T cell interactions are modulated by chemokines. In B cell malignancies, these interactions may have tumor-promoting consequences. Areas covered: This review summarizes physiological B cell–T cell interactions and discusses their pathological role in the onset and progression of B cell malignancies with a special focus on chronic lymphocytic leukemia and multiple myeloma. Experimental data on chemokine-guided B cell-T cell actions in B cell malignancies from murine models as well as in vitro data are summarized and their potential as future therapeutic targets is critically discussed. Expert opinion: Direct or indirect targeting of chemokine receptors involved in localization and T-cell-dependent activation of B lymphocytes can provide strong synergisms with conventional or immunomodulatory therapies by disrupting the microenvironmental conditions necessary for survival and proliferation of malignant B lymphocytes. However, further knowledge of these interactions between B and T cells is needed.
The effect of a cycling stage race on whole-body protein turnover

Abstract Marked energy expenditure, independent of energy balance, could change whole-body protein turnover. The aims of the present study were to determine the effect of participation in a 6-day, 10-stage cycling stage tour on whole-body protein turnover in elite male cyclists, and to determine whether energy and protein turnover are related to fatigue and over-reaching. 13C-leucine was used to determine 18-h whole-body protein turnover in cyclists both before and immediately after a cycling stage race. The 18-h period included two feeding periods to simulate a normal evening meal and a normal breakfast meal, and two fasted periods including overnight. Blood was drawn for the determination of plasma cortisol and serum ferritin on days 2, 4, and 6 and a Profile of Mood States questionnaire was administered on alternate days during the tour event for determination of markers of over-reaching. Mean leucine rate of appearance was unchanged from pre- to post-tour during both fed and fasted conditions and mean energy balance was maintained. Serum ferritin concentration declined and plasma cortisol concentration remained stable over the 6 days. Markers of overtraining were evident in one athlete who pulled out of the tour event due to fatigue on the second to last day. Our main finding was that high energy output over a 6-day period did not significantly change protein turnover during fed, fasted or overnight conditions.