Miracle-dz/UniFAR-FTUs huggingface dataset:
Reversing neuromuscular blockade: inhibitors of the acetylcholinesterase versus the encapsulating agents sugammadex and calabadion

ABSTRACT Introduction: Acetylcholinesterase inhibitors (neostigmine, edrophonium) and encapsulating agents (sugammadex and calabadion) can be used to reverse residual neuromuscular blockade (NMB). Areas covered: This review provides information about efficacy, effectiveness, and side effects of drugs (acetylcholinesterase inhibitors and encapsulating agents) used to reverse neuromuscular blocking agents (NMBAs). Expert opinion: The therapeutic range of acetylcholinesterase-inhibitors is narrow and effectiveness studies demonstrate clinicians don’t use these unspecific reversal agents effectively to increase postoperative respiratory safety. The encapsulating drugs sugammadex and calabadion reverse all levels of NMB, and complete recovery of muscle strength can be achieved almost immediately after administration. For this reason encapsulating agents can be used as a solution for “cannot intubate cannot ventilate”- situations. Poor binding selectivity of encapsulating agents carries the risk of displacement of the NMBA by a competitively binding drug, which may lead to recurarization. In order to avoid side-effects, related to unspecific binding of endogenous proteins and drugs administered perioperatively it is prudent to titrate the dose of reversal agents to the minimal effective dose, depending on the depth of neuromuscular transmission block identified by neuromuscular transmission monitoring. Calabadions provide a diversified (increased binding selectivity) and expanded (reversal of benzylisoquinolines) spectrum of possible indications.
Review: Health literacy intervention and their consequences

Health literacy is one of the most critical issues threating the public health today and there are significant gaps behind the discipline of health literacy. Low health literacy was found to threaten the health and welfare of people. The past decades witnessed a revolutionary alteration in the health patterns and disease spread among the community from infectious diseases to chronic diseases such as, heart disease, stroke, cancer, diabetes and accidents. Furthermore, to enhance health status among the population with effective intervention methods, through health teaching, increasing access to health information and communication technologies will eliminate the health literacy consequences among different community levels, including children and adults. The aim of the present review was to find out the current status about research progress towards health literacy. Furthermore, to examine health literacy status, intervention, possible consequences and future prospective, and to find out the options for improving health literacy status and fill in the future research. A systematic review based on literature research related to health literacy covered the recent publication from 2000 to 2014 years. The results indicated that the wide range opportunities for improving health literacy are coming through health literacy intervention among target community. Future research concerning health literacy is still needed to give much more efforts in the field of community and community health works. Key words: Health literacy, intervention, knowledge and community health.
Atraso na busca por serviço de saúde para o diagnóstico da tuberculose em Ribeirão Preto (SP)

The scope of this paper is to analyze delays in locating health services for the diagnosis of tuberculosis in Ribeirao Preto in 2009. An epidemiological and cross-sectional study was conducted with 94 TB patients undergoing treatment. A structured questionnaire, based on the Primary Care Assessment Tool adapted for TB care was used. A median (15 days or more) was established to characterize delay in health attendance. Using the Prevalence Ratio, the variables associated with longer delay were identified. The first healthcare services sought were the Emergency Services (ES) (57.5%). The longest period between seeking assistance occurred among males, aged between 50 and 59, who earned less than five minimum wages, had pulmonary TB, were new cases, were not co-infected with TB/HIV, did not consume alcohol, had satisfactory knowledge about TB before diagnosis (with a statistically significant association with delay) and who did not seek healthcare close to home before developing TB. There is a perceived need for training healthcare professionals about the signs and symptoms of the disease, reducing barriers of access to timely diagnosis of TB and widely disseminating it to the community in general.
Leishmaniasis mucocutánea con afectación laríngea

La leishmaniasis es la infeccion producida por protozoos del genero Leishmania. Presenta diferentes formas clinicas, dentro de las cuales, la leishmaniasis mucocutanea es una de las que conlleva mayor gravedad debido al compromiso de la via aerea superior, que puede producir secuelas incapacitantes e incluso la muerte. Presentamos el caso de un paciente con diagnostico de leishmaniasis mucocutanea con importante compromiso laringeo, el cual tuvo excelente respuesta al tratamiento con antimoniales pentavalentes.
Chronic lymphocytic leukemia therapy: new targeted therapies on the way

ABSTRACT Introduction: The critical role of the tissue microenvironment and B-cell receptor (BCR) signaling in chronic lymphocytic leukemia (CLL) pathogenesis, and the clinical success of targeted agents that disrupt BCR signaling are currently changing the CLL landscape. Three new drugs were recently approved for CLL therapy, and other agents are in late development. Areas covered: In this review, we summarize data on promising new targeted drugs for CLL. The heterogeneous mechanisms of actions of these molecules are described, such as the inhibition of BCR signaling, direct targeting of CD20 molecules on the CLL cell surface, and BCL-2 inhibition. We present preclinical and clinical data from phase I to III studies in order to describe efficacy and side effect profile of these new drugs. Data are derived from peer-reviewed articles indexed in PubMed and from abstracts presented at major international meetings. Expert opinion: Ibrutinib and idelalisib are challenging the role of chemo-immunotherapy in CLL therapy in the frontline and relapsed disease settings. High-risk CLL patients particularly benefit from these new agents. Venetoclax and obinutuzumab are other effective agents added to our therapeutic armamentarium. Studies to better define the optimal use of these drugs, alone, or rather in combination or sequenced are underway.
APOE ε2/ε4 polymorphism and cerebral microbleeds on gradient-echo MRI

The association of APOE genotypes with cerebral microbleeds (CMBs) was examined on the basis of the location of CMBs in 414 patients who were admitted primarily because of stroke. With respect to possession of the ε2 or ε4 allele, the adjusted odds ratio was 1.94 (1.05 to 3.58) for lobar CMBs but 1.21 (0.69 to 2.11) for nonlobar CMBs. This suggests that the pathogenesis of CMBs may differ depending on their location.
Adoptive T cell immunotherapy for cytomegalovirus

Cytomegalovirus (CMV) is a major opportunistic pathogen following allogeneic transplantation, reflecting the inability of depressed host immunity to contain viral replication. Current antiviral drugs are limited by toxicities and lack of efficacy in established CMV disease, making adoptive immunotherapeutic strategies aimed at hastening virus-specific immune reconstitution attractive alternatives. A number of relatively small Phase I-II studies have demonstrated the feasibility of transferring CMV-specific T cells, varying in composition in terms of CD4+ and CD8+ T cell content. They have all suggested to varying degrees that restoration of CMV-specific immunity can be accelerated without an obvious effect on rates of graft-versus-host disease in those with CMV-seropositive donors. The majority also infer that recovery of laboratory measures of CMV-specific immunity correlate with clinical protection. Direct isolation of cells from donor blood now allows consideration of more widespread availability outside of a few academic centres, and equally importantly the delivery of randomised studies to establish the true efficacy of these strategies.
Cytokine induced killer cells as adoptive immunotherapy strategy to augment graft versus tumor after hematopoietic cell transplantation

Donor lymphocyte infusion (DLI) is used to increase the graft versus tumor (GVT) effect after allogeneic hematopoietic cell transplant (HCT). The limited spectrum of activity and high risk of graft versus host disease (GVHD) remain major limitations of this approach. The finding of new cell populations for adoptive immunotherapy, with the ability to separate GVT from GVHD, would be useful. Here we review the main basic, preclinical and clinical research on cytokine-induced killer (CIK) cells, highlighting the aspects of their antitumor and alloreactive potentials that might favourably affect the balance between GVT and GVHD. CIK cells are ex vivo-expanded T lymphocytes sharing NK markers and endowed with a potent MHC-unrestricted antitumor activity against haematological and solid malignancies. Studies in preclinical animal models have demonstrated their low GVHD potential when infused across MHC-barriers, and recent clinical studies seem to confirm these findings in patients with hematological malignances relapsing after HCT. If consolidated with larger clinical trials, adoptive immunotherapy with CIK cells might represent an effective alternative to classic DLI, helping HCT to succesfully meet current challenges like the extension across major HLA-barriers and application to solid tumors.
Anticomplement activity of various solvent extracts from Korea local Artemisia spp.

The study evaluated the anticomplement activity from various solvent extracts of eight Artemisia plants (Artemisia capillaris Thunb., Artemisia fukudo Makino., Artemisia japonica Thunb., Artemisia montana (Nakai) Pamp. , Artemisia keiskeana Miq. , Artemisia rubripes Nakai. , Artemisia stolonifera (Maxim.) Kom. , and Artemisia sylvatica Max.) from South Korea on the classical pathway (CP). We have evaluated various organic solvent extract from eight Artemisia plants with regard to its anticomplement activity on the CP. A. rubripes and A. montana chloroform extracts showed inhibitory activity against complement system with 50% inhibitory concentrations (IC50) values of 54.3 and 64.2 μg/mL. This is the first report of anticomplement activity from Artemisia plants.
The dawn of hedgehog inhibitors: Vismodegib

Cancer, one of the leading causes of death worldwide is estimated to increase to approximately 13.1 million by 2030. This has amplified the research in oncology towards the exploration of novel targets. Recently there has been lots of interest regarding the hedgehog (Hh) pathway, which plays a significant role in the development of organs and tissues during embryonic and postnatal periods. In a normal person, the Hh signaling pathway is under inhibition and gets activated upon the binding of Hh ligand to a transmembrane receptor called Patched (PTCH1) thus allowing the transmembrane protein, smoothened (SMO) to transfer signals through various proteins. One of the newer drugs namely vismodegib involves the inhibition of Hh pathway and has shown promising results in the treatment of advanced basal-cell carcinoma as well as medulloblastoma. It has been granted approval by US Food and Drug Administration's (US FDA) priority review program on January 30, 2012 for the treatment of advanced basal-cell carcinoma. The drug is also being evaluated in malignancies like medulloblastoma, pancreatic cancer, multiple myeloma, chondrosarcoma and prostate cancer. Moreover various Hh inhibitors namely LDE 225, saridegib, BMS 833923, LEQ 506, PF- 04449913 and TAK-441 are also undergoing phase I and II trials for different neoplasms. Hence this review will describe briefly the Hh pathway and the novel drug vismodegib.
Teaching and learning geriatric medicine

Populations throughout the world are ageing, with the oldest old the most rapidly growing segment of society. Caring for this ageing population, some of whom have multiple chronic and disabling diseases, will be challenging to healthcare systems. Current training programmes are generating relatively low numbers of geriatricians, largely because students and residents lack interest in a career in geriatric medicine. Therefore, specialists in geriatric medicine cannot directly provide care for all older people. There is a responsibility to ensure that successful practices and essential skills are shared. Here we explore negative attitudes towards geriatric medicine and contrast these with factors motivating change. Educational theories are discussed to investigate how processes of learning and the personal development of students can be optimized. An understanding of geriatric medicine is important for undergraduates, postgraduate trainees in geriatric medicine, general practitioners and allied health professionals. The different challenges presented by each group are reviewed, accompanied by recommendations to enhance learning and examples of effective teaching practices.
HPV vaccine: Cervarix

Importance of the field: Cervical cancer is a major cause of morbidity and mortality worldwide and is common in relatively young women. Cervical screening programs, while successful if properly carried out, are difficult and expensive to implement, and offer secondary, not primary prevention. Vaccination against the human papillomavirus (HPV), which is the major cause of cervical cancer, is a significant step forward. Areas covered in this review: The data on Cervarix, the GSK HPV vaccine, are reviewed and placed in the context of HPV vaccination as a whole. A literature review using PubMed listed publications and official product websites has been carried out. What the reader will gain: The reader will gain an understanding of the issues involved in HPV vaccination and of the data to date. Take home message: Cervarix has been shown to have high efficacy against disease associated with both HPV-16 and HPV-18. Its antibody response profile allows for optimism regarding the duration of immunity. The fact that it is a virus-like particle, rather than a live-virus vaccine, is reassuring regarding safety, as are the reasonably extensive safety data for the vaccine preparation so far accrued. Cross protection against oncogenic non-vaccine HPV types, in particular HPV-45, may be important in the prevention of cervical adenocarcinoma, which is currently not well served by screening.
Cross reaction between proteins from Larrea divaricata Cav. (jarilla) and cellular and extracellular proteins of Pseudomonas aeruginosa

Larrea divaricata is widely used in folk medicine to treat different pathologies, but little is known about its immunological properties. Pseudomonas aeruginosa is an opportunistic pathogen which causes several intrahospitalary infections. We aimed to assess the immunological relation between proteins from a crude extract of L. divaricata Cav. (JPCE) and cellular and extracellular proteins (EP) of P. aeruginosa, as well as to establish the cross reactivity between proteins of both species using a mouse anti-JPCE serum. Protein profiles of JPCE and P. aeruginosa were analyzed by SDS-PAGE. The percentage of similarity of protein bands between these two species was 43–57%. However, JPCE proteins were immunogenic. The reactivity of mouse anti-JPCE antibodies against different fractions was studied by western blot. The anti-JPCE serum detected several antigenic bands on different bacterial proteins. Several common immunoreactive bands were detected (27–100%) when bacterial proteins were incubated with anti-JPCE serum (heterologous reaction) and anti-bacterial proteins serum (homologous reaction). By enzyme-linked immunosorbant assay (ELISA) assays, high titers of anti-JPCE against different types of cellular bacterial fractions were observed (1/1280–1/2080). Our data clearly demonstrate that antibodies elicited with L. divaricata crude extract are able to cross-react with cellular and EP of P.aeruginosa. These findings could be relevant in the development of alternatives therapies for patients suffering intrahospitalary opportunistic infections with P.aeruginosa.
Microenvironmental targeting of Wnt/β-catenin signals for hematopoietic stem cell regulation

Importance of the field: Microenvironment has emerged as crucial element in the regulation of hematopoietic stem cells (HSCs) in the stem cell niche. Recent studies have demonstrated that Wnt/β-catenin signals are clearly involved in the stem cell niche, raising the possibility that the hematopoietic microenvironment is a potential target for stem cell therapy. Areas covered in this review: In this review, the biological outcomes of Wnt/β-catenin signals on HSC activity are summarized in various study models and potential reasons for discrepancies are discussed. Evidence for the microenvironmental targeting of Wnt/β-catenin signals and studies that verify this concept is summarized. What the reader will gain: We show that distinct effects of Wnt/β-catenin on HSCs can be caused depending on their target of activation in the hematopoietic microenvironment. We show stromal targeting of Wnt/β-catenin signals and cross-talk with notch signals in the niche during bone marrow regeneration enhancing the self-renewal of HSCs. Take home message: The identification of stroma-mediated Wnt/β-catenin effects now allows the integration of discrepancies in previously reported findings and suggests that the stromal targeting of wnt/β-catenin signals could serve as a potential therapeutic strategy for activating a stem cell niche for the efficient regeneration of HSCs.
Pemberian Ekstrak Benalu Mangga terhadap Perubahan Histologis Hepar Tikus yang Diinduksi Kodein

Benalu mangga mengandung senyawa kuersetin yang bertindak sebagai hepatoprotektor. Kodein merupakan jenis alkaloid dan banyak digunakan sebagai obat. Oversdosis kodein dapat menyebabkan kerusakan hepar. Penelitian ini bertujuan untuk mengetahui pengaruh pemberian ekstrak benalu mangga terhadap perubahan histologis hepar tikus yang diinduksi kodein. Sebanyak 20 ekor tikus wistar jantan dibagi menjadi 5 kelompok (K0, K, KB1, KB2, dan KB3). Kelompok K0 hanya diberi minum dan pakan standar, kelompok K diberi kodein 12mg/ekor selama 7 hari, selanjutnya hanya diberi pakan dan minum standar. Kelompok KB1 diberi kodein 12mg/ekor selama 7 hari dilanjutkan ekstrak benalu mangga 22mg/ekor sampai hari ke 21, kelompok KB2 diberi kodein 12mg/ekor selama 7 hari dilanjutkan ekstrak benalu mangga 44mg/ekor sampai hari ke 21, dan kelompok KB3 diberi kodein 12mg/ekor selama 7 hari dilanjutkan ekstrak benalu mangga 88mg/ekor sampai hari ke 21.Hari ke-27 semua tikus dibedah, diambil heparnya dan dibuat preparat histologi dengan pengecatan HE. Hasil penelitian kelompok K0 menunjuk k an perubahan histologis hepar bermakna (p 0,05) antara K,KB1, KB2, dan KB3. Pada kelompok K kerusakan struktur hepar meliputi inflamasi perportal dan degenerasi sedangkan pada kelompok KB1, KB2, dan KB3 kerusakan meliputi inflamasi periportal,degenerasi, dan nekrosis. Mango’s mistletoes contain quercetin, a hepatoprotector. Codein is a type of alkaloids widely used as drug. Codein overdose can damage the liver. The objective of the study was know the effect of the administration of extract of mango’s mistletoes on the changes of liver histology of codein-induced rats. As many as 20 male wistar rats were divided into 5 groups (K0, K, KB1, KB2, and KB3). K0 group were given only standard diet and water daily. K group were given codeine at 12mg/rats for 7 days, and afterwards they were given only standard diet and water daily. KB1 group were given codeine at 12mg/rats for 7 days and then were given extract of mango’s mistletoes at 22 mg/rats until day 21, KB2 group were given codeine at 12mg/rats for 7 days and then were given extract of mango’s mistletoes at 44 mg/rats until day 21, and KB3 group were given codeine at 12mg/rats for 7 days and were given extract of mango’s mistletoes at 88 mg/rats until day 21. At day 27, all rats were killed, the livers were taken out for preparations with HE staining for histology examination. Research showed that K0 group was significantly different (p <0.05) to K, KB1, KB2, and KB3 groups, whereas K group was not significantly different to KB1, KB2 and KB3 groups. Rats in K group showed the changes in histological appearance such as periportal inflammation and degeneration, whereas rats in KB1, KB2, KB3 groups showed similar histological appearance but with necrosis.
Consumer perceptions of seasonal and local foods: A study in a U.S. community

Food descriptors like local, seasonal, farm-fresh, or home grown convey a connection to place and time. Little is known about how U.S. consumers conceptualize local and seasonal as applied to foods. Using a questionnaire, 120 shoppers in a grocery store and a food cooperative were surveyed. Shoppers were asked to describe the concepts of local foods and seasonal foods and to name foods that were local, not local, seasonal, and not seasonal. The concept of seasonal was multidimensional and had more meanings than the concept of local. Many foods named as local were fruits and vegetables, and many not local foods were tropical fruits. Many foods named as seasonal were fruits and vegetables, and many named as not seasonal were staple foods like meat, breads, and cereals. Locality and seasonality have specific agricultural meanings, and clarifying consumer meanings may be important in food marketing and community food systems. As the food system becomes increasingly global and decreasingly seasonal, consciousness about local and seasonal foods has implications for community economic development, environmental sustainability, human nutrition, and the operation of food markets.
Stromal cell-derived factor-1 (SDF-1): homing factor for engineered regenerative medicine

Introduction: Stromal cell-derived factor-1α (SDF-1) is a chemokine that plays a major role in cell trafficking and homing of CD34+ stem cells. Studies employing SDF-1/CXCR4 have demonstrated its therapeutic potential in tissue engineering. During injury, cells from the injured organ highly express SDF-1, which causes an elevation of localized SDF-1 levels. This leads to recruitment and retention of circulating CD34+ progenitor cells at the injury site via chemotactic attraction toward a gradient of SDF-1. The general approaches for SDF-1 introduction in tissue engineering are direct protein incorporation into scaffolds and transplantation of SDF-1-overexpressing cells and both methods are successful in improving the regeneration of the damaged tissue/organ. Areas covered: The mechanisms of SDF-1-mediated homing via CXCR4 receptor and the success of SDF-1-based medical applications in mesenchymal stem cell (MSC) homing as well as areas such as therapeutic angiogenesis, wound healing and neuronal and liver regeneration. Expert opinion: Current SDF-1 delivery designs and platforms hold much room for improvement. Regardless of the different techniques of SDF-1 introduction, they have proved to be effective in recruitment of various stem/progenitor cells. The pursuit of SDF-1-related regenerative medicine has already begun. It is thus conceivable that its usage in the clinical setting will be a reality in the near future.