Miracle-dz/UniFAR-FTUs huggingface dataset:
Genistein inhibited proliferation and induced apoptosis in acute lymphoblastic leukemia, lymphoma and multiple myeloma cells in vitro

Abstract Genistein is one of the major isoflavones in soy products. It has been reported that genistein has apoptotic effects on certain hematological malignancies. However, so far there have been no completely comparative studies of the effect of genistein on malignant hematological diseases, especially multiple myeloma. We investigated genistein's inhibitory effect on the growth of acute lymphoblastic leukemia (RS4;11 and CEM), lymphoma (Toledo and GA10) and multiple myeloma (OPM-2 and U266) cell lines in vitro. We observed that genistein dose- and time-dependently inhibited proliferation of these cells. The cell line sensitivity to genistein treatment based on the 50% inhibitory concentration (IC50) values in decreasing order of toxicity was found to be as follows: RS4;11 (4.89 ± 4.28 μM) > GA10 (13.08 ± 3.49 μM) > Toledo (16.94 ± 3.89 μM) > CEM (17.31 ± 0.72 μM) > OPM-2 (46.76 ± 2.26 μM) > U266 (128.82 ± 1.90 μM). The mechanism of growth inhibition was through induction of apoptosis and cell cycle arrest. The concomitant altered expression of apoptosis pathway proteins and cell cycle modulators (caspases 9, 3, 7, PARP [poly(ADP-ribose) polymerase], cIAP1 [inhibitor of apoptosis protein 1], Bcl-2 and cyclin B1) were observed by Western blot and real-time polymerase chain reaction (PCR) analyses. In addition, some malignancy-related embryologic pathway proteins, e.g. Notch1 and Gli1, were modulated by genistein treatment in sensitive cell lines.
Genetic association and functional role of Crohn disease risk alleles involved in microbial sensing, autophagy, and endoplasmic reticulum (ER) stress

Genome-wide association studies have identified several genes implicated in autophagy (ATG16L1, IRGM, ULK1, LRRK2, and MTMR3), intracellular bacterial sensing (NOD2), and endoplasmic reticulum (ER) stress (XBP1 and ORMDL3) to be associated with Crohn disease (CD). We studied the known CD-associated variants in these genes in a large cohort of 3451 individuals (1744 CD patients, 793 ulcerative colitis (UC) patients and 914 healthy controls). We also investigated the functional phenotype linked to these genetic variants. Association with CD was confirmed for NOD2, ATG16L1, IRGM, MTMR3, and ORMDL3. The risk for developing CD increased with an increasing number of risk alleles for these genes (P < 0.001, OR 1.26 [1.20 to 1.32]). Three times as many (34.8%) CD patients carried a risk allele in all three pathways, in contrast to 13.3% of the controls (P < 0.0001, OR = 3.46 [2.77 to 4.32]). For UC, no significant association for one single nucleotide polymorphism (SNP) was found, but the risk for development of UC increased with an increasing total number of risk alleles (P = 0.001, OR = 1.10 [1.04 to 1.17]). We found a genetic interaction between reference SNP (rs)2241880 (ATG16L1) and rs10065172 (IRGM) in CD. Functional experiments hinted toward an association between an increased genetic risk and an augmented inflammatory status, highlighting the relevance of the genetic findings.
Consensus Statement on the Triage of Critically III Patients

The demand for medical services such as critical care is likely to often exceed supply. In the setting of these constraining conditions, institutions and individual providers of critical care must use some moral framework for distributing the available resources efficiently and equitably. Guidelines are therefore provided for triage of critically ill patients. There are several general principles that should guide decision making: providers should advocate for patients; members of the provider team should collaborate; care must be restricted in an equitable system; decisions to give care should be based on expected benefit; mechanisms for alternative care should be planned; explicit policies should be written; prior public notification is necessary. Patients who are not expected to benefit from intensive care, such as those with imminently fatal illnesses or permanent unconsciousness, should not be placed in the intensive care unit. Hospitals should assign individuals the responsibility of intensive care triage, and a committee should oversee the performance of this responsibility to facilitate the most efficient and equitable use of intensive care. ( JAMA . 1994;271:1200-1203)
The membrane peroxin PEX3 induces peroxisome-ubiquitination-linked pexophagy

Peroxisomes are degraded by a selective type of autophagy known as pexophagy. Several different types of pexophagy have been reported in mammalian cells. However, the mechanisms underlying how peroxisomes are recognized by autophagy-related machinery remain elusive. PEX3 is a peroxisomal membrane protein (PMP) that functions in the import of PMPs into the peroxisomal membrane and has been shown to interact with pexophagic receptor proteins during pexophagy in yeast. Thus, PEX3 is important not only for peroxisome biogenesis, but also for peroxisome degradation. However, whether PEX3 is involved in the degradation of peroxisomes in mammalian cells is unclear. Here, we report that high levels of PEX3 expression induce pexophagy. In PEX3-loaded cells, peroxisomes are ubiquitinated, clustered, and degraded in lysosomes. Peroxisome targeting of PEX3 is essential for the initial step of this degradation pathway. The degradation of peroxisomes is inhibited by treatment with autophagy inhibitors or siRNA against NBR1, which encodes an autophagic receptor protein. These results indicate that ubiquitin- and NBR1-mediated pexophagy is induced by increased expression of PEX3 in mammalian cells. In addition, another autophagic receptor protein, SQSTM1/p62, is required only for the clustering of peroxisomes. Expression of a PEX3 mutant with substitution of all lysine and cysteine residues by arginine and alanine, respectively, also induces peroxisome ubiquitination and degradation, hence suggesting that ubiquitination of PEX3 is dispensable for pexophagy and an endogenous, unidentified peroxisomal protein is ubiquitinated on the peroxisomal membrane.
Pyogenic Liver Abscess Mimicking Liver Neoplasm on Computed Tomography Scan in a Patient With Elevated CA 19-9

Pyogenic liver abscess (PLA) presentation on computer tomography (CT) scan depends mainly on the degree of maturation and internal contents, but rarely presents similarly to primary liver cancer (PLC) or hepatic metastasis. However, distinguishing PLA from PLC can be a challenge, and several cases were reported previously where tumor markers helped in this differentiation. We present a rare case of PLA with radiological findings similar to PLC or liver metastasis on CT scan in a patient with elevated tumor marker, carbohydrate antigen (CA) 19-9. This case illustrates that a combination of risk factors and clinical findings including localizing symptoms, fever, leukocytosis and tumor markers has to accompany image findings to reach an appropriate differentiation in a query case of hepatic lesion. J Med Cases. 2015;6(8):346-349 doi: http://dx.doi. org/10.14740/jmc2238w
The impact of a traumatic birth injury on the internal world of an adult patient: a self-psychological psychoanalysis.

This paper shows how Heinz Kohut’s formulations were particularly relevant to the treatment of a patient whose cranial injury at birth became a catalyst for rejections that resulted in a demeaned view of himself, compulsive sexual behavior, and suicidal ideation. The potential negative psychological effects and negative social impact of facial deformity have been well documented (see especially Berger, 1973; Coulter, Scheuerle, Laude, & Habal, 1991; Crocker & Major, 1989; Hill-Beuf & Porter, 1984; Lansdown, Lloyd, & Hunter, 1991; Pruzinsky, 1992). Four problem areas where patients may be particularly affected are (1) cognitive development in the case of severe craniofacial anomalies, (2) the emotional attachment between the child and parents, (3) development of peer relations and, (4) the experience of shame (Pruzinsky, 1992). A major risk for children who have impaired appearance is their being labeled as deviant and stigmatized by society in general. Hill-Beuf and Porter (1984) point out that there is an intolerant attitude in the United States toward children with impaired appearance and conclude that the culture attributes tremendous importance to a narrow standard of beauty. While people who suffer deformity are faced with potentially devastating stressors, there is no way to predict whether a particular individual will develop psychological problems (Lansdown et al., 1991). Each of these individuals will respond uniquely according to life situations and capacities to make adjustments. Self psychology is especially helpful in this regard. The theory of the self, formulated by Heinz Kohut, is founded on the fact that
A Journal of the Plague Year

148 pp. This Renascence Edition was transcribed by Risa Stephanie Bear, February, 2008, from the text as found in A Journal of the/Plague Year/Being Observations or Memorials/of the most Remarkable Occurences, as/well Publick as Private, which/happened in London during/the last Great Visitation in 1665/Written by a Citizen who continued all the/while in London. Never made publick before, Volume 6 of The Shakespeare Head edition of the novels and selected writings of Daniel Defoe. Oxford, Blackwell, 1927.
The autophagosomal protein LGG-2 acts synergistically with LGG-1 in dauer formation and longevity in C. elegans

Autophagy has an important function in degrading cytoplasmic components to maintain cellular homeostasis, but is also required during development. The formation of the autophagic vesicles requires the recruitment of the Atg8 ubiquitin-like proteins to the membrane of the nascent autophagosomes. Atg8 is a highly conserved gene which has been duplicated during metazoan evolution. In this report we have investigated, in the nematode C. elegans, the functions and localizations of the two Atg8p homologues LGG-2 and LGG-1. Phylogenetic analyses suggest that LGG-2 is more closely related to the human protein LC3 than LGG-1. LGG-1 but not LGG-2 is able to functionally complement the atg8 mutant yeast. The C-terminal glycine residue of LGG-2 is essential for post-translational modification and localization to the autophagosomes. During C. elegans development the two proteins share a similar expression pattern and localization but LGG-2 is more abundant in the neurons. Using genetic tools to either reduce or increase the autophagic flux we show that both LGG-2 and LGG-1 are addressed to the autophagosomal/lysosomal degradative system. We also demonstrate that the localization of both proteins is modified in several physiological processes when autophagy is induced, namely during diapause “dauer” larval formation, starvation and aging. Finally, we demonstrate that both LGG-2 and LGG-1 act synergistically and are involved in dauer formation and longevity of the worm.
Falling into sexuality: sexual boundary violations in psychotherapy.

class of women with whom this attempt to preserve the erotic transference for the purposes of analytic work without satisfying it will not succeed. These are women of elemental passionateness who tolerate no surrogates. [In such cases it is not] always easy for the doctor to keep within the limits prescribed by ethics and technique. Again, when a woman sues for love, to reject and refuse is a distressing part for a man to play; and, in spite of neurosis and resistance, there is an incomparable fascination in a woman of high principles who confesses her passion (Freud, 1915, pp. 166–170)
Gigantic macroautophagy in programmed nuclear death of Tetrahymena thermophila

Programmed nuclear death (PND) in Tetrahymena is a unique process during conjugation, in which only the parental macronucleus is degraded and then eliminated from the progeny cytoplasm, but other co-existing nuclei such as new micro- and macronuclei are unaffected. PND through autophagic elimination is expected to be strictly controlled, considering the significant roles in ciliates such as turnover of disused organelles and production of the next generation. Here we demonstrate that PND in Tetrahymena involves peculiar aspects of autophagy, which differ from mammalian or yeast macroautophagy. Drastic change of the parental macronucleus occurs when differentiation of new macronuclei is initiated. Combined use of monodansylcadaverine and a lysosome indicator LysoTracker Red showed that prior to nuclear condensation, the envelope of the parental macronucleus changed its nature as if it is an autophagic membrane, without the accumulation of a pre-autophagosomal structure from the cytoplasm. Subsequently, lysosomes approached only to the parental macronucleus and localized at the envelope until a final resorption stage. In addition, we found that the parental macronucleus exhibits certain sugars and phosphatidylserine on the envelope, which are possible "attack me" signals, that are not found on other types of nuclei. These findings suggest that PND is a highly elaborated process, different from the typical macroautophagy seen in other systems, and is executed through interaction between specific molecular signals on the parental macronuclear envelope and autophagic/lysosomal machineries.
Plasma membrane helps autophagosomes grow

The membrane origin of autophagosomes has long been a mystery and it may involve multiple sources. In this punctum, we discuss our recent finding that the plasma membrane contributes to the formation of pre-autophagic structures via clathrin-mediated endocytosis. Our study suggests that Atg16L1 interacts with clathrin heavy-chain/AP2 and is also localized on vesicles (positive for clathrin or cholera toxin B) close to the plasma membrane. Live-cell imaging studies revealed that the plasma membrane contributes to Atg16L1-positive structures and that this process and autophagosome formation are impaired by knockdowns of genes regulating clathrin-mediated endocytosis.
Working Conditions in Home Care: Comparing Three Groups of Workers

RÉSUMÉ Cette étude porte sur les similitudes et les différences entre les méthodes de soins utilisées par trois groupes de prestateurs de soins, soit les proches parents, les femmes au foyer et les bénévoles. Dans le contexte des conditions de travail, des questions ayant trait au milieu de travail, à l'isolement, à la communication, aux réactions, à l'autonomie, à la motivation et au choix font l'objet d'une comparaison au sein de ces trois groupes. Même si les capacités fonctionnelles des personnes âgées bénéficiant des soins étaient semblables, les circonstances touchant la prestation de soins variaient beaucoup. L'étude démontre que le contexte au sein duquel les soins sont prodigués représente un élément clé dans le cadre de discussions futures en matière d'établissement de politiques. Elle suggère que les tâches particulières relatives à la prestation de soins ne sont qu'un élément secondaire servant à comprendre le contexte dans lequel chaque prestateur de soins accomplit son travail. ABSTRACT This paper explores similarities and differences in the way caring work is experienced by kin, homemakers and volunteers. Under the conceptual umbrella of working conditions, issues of work milieu, isolation, communication, feedback, autonomy, motivation and choice are compared across these three groups of care providers. Although the functional capacities of the elderly persons receiving care were quite similiar, the circumstances that surrounded the performance of caring were quite different. The paper argues that the context within which care is provided will be critical in future policy discussions. It is suggested that the specific task content of providing care may be of secondary importance to understanding the context within which care providers carry out these activities.
Impacto económico de la peste bubónica en Cajamarca - Perú¹

Objectives: To determine the economic impact of plague in three provinces of Cajamarca department in 1994 and 1999. Materials and methods: In this observational, cross-sectional and descriptive study, we estimated the direct and indirect costs (institutional, familial, and community costs) of plague in San Miguel, San Pablo, and Contumaza Provinces in Cajamarca Department for 1994 and 1999. Data for cost calculation was obtained from different sources: data compilation, interviews to health care workers and/or directors or managers of health institutions and health facilities, home surveys, etc. Results: In 1994, the total estimated cost of plague rose to US$ 2´333,169. This cost was divided as follows: MINSA (Ministry of health, working materials) (US$ 65,034), MINSA-direct attention (US$ 81,388), institutional cost (US$ 106,428), family cost (US$ 663,449), and mortality cost (US$1´416,870). In 1999, the total cost rose to US$ 741,431, and it was divided as follows: MINSA ‐ working materials (US$ 322,371), MINSA-direct attention (US$ 34,063), institutional cost (US$ 15,477), family cost (US$ 369,550) and no cost for mortality. Conclusions: Plague has a high cost for the regional economy of Peru, and there are annual costs variations, according to the disease behavior and the policies for its control and prevention.
Effect Of Ginger Infusion On Chemotherapy Induced Nausea And Vomiting In Breast Cancer Patients

Nausea and vomiting are the most common side effects of chemotherapy. Ginger is one of complementary therapy to treat nausea and vomiting. The purpose of this study was to determine the effect of ginger infuse for nausea and vomiting side effects of chemotherapy in breast cancer patients. Control Time Series Design was used to collect the data. Purposive sampling technique was used to get sample with total sample was 20 people. Rhodes Index Nausea Vomiting and Reching were used for scaling nausea and vomiting. Therapy was given from second until sixth day after chemotherapy. Data analized with Friedman Test and Mann-Whitney Test. The results of this study showed that the significant decreased of nausea and vomiting in experimental group (p = 0.000) is better than control grup (p=0,011). Differences nausea vomiting experimental group and the control group significant with value of p = 0.036. It is recommended to use ginger as a complementary therapy in the management of Chemotherapy Induced Nausea and Vomiting. Keyword s: ginger , complementary therapy, nausea, vomiting, chemotherapy, breast cancer
The mRNA Expression of Cyclo-oxygenase-2 (COX-2) and Vascular Endothelial Growth Factor (VEGF) in Human Breast Cancer

Summary Aims: There is a growing body of evidence that cyclo-oxygenase 2 (COX-2) plays an important role in carcinogenesis and angiogenesis of human tumours. The present study aims to compare COX-2 expression in human breast cancer and adjacent non-cancerous tissue (ANCT), and to identify any correlation between COX-2 and VEGF expression. Methods: Total cellular RNA was extracted from frozen breast tissue samples according to standard methodology. The mRNA copy numbers for COX-2 and vascular endothelial growth factor 189 (VEGF-189) were determined 40 infiltrating carcinomas and 40 matched ANCT specimens using quantitative RT-PCR and TaqMan methodology. Results: The COX-2 mRNA copy number per ixg of RNA was two-fold higher in ANCT compared with the cancerous tissue (p = 0.01). Median mRNA copy number was 5.44 x 106 for ANCT and 2.30 x 106for tumour, (ANCT range: 1 x 106to4.12x 107) (tumour range: 1.29 x 105to1.07x 107). There was a significant correlation between COX-2 and VEGF-189 mRNA copy numbers in the cancer specimens (correlation coefficient = 0.5528, p = 0.0076). Conclusions: COX-2 mRNA is overexpressed in both human breast cancer and ANCT. We found higher levels in the matched ANCT which suggests that paracrine effects may be important in the role of COX-2 in mammary carcinogenesis. Furthermore, our results indicate that in human breast cancers COX-2 overexpression is linked to VEGF-189 overexpression and therefore tumour angiogenesis.
Immunization trials with an avian chlamydial MOMP gene recombinant adenovirus

Avian chlamydiosis (AC) is an infectious disease caused by Chlamydophila psittaci. Named after psittacosis or ornithosis, the bacterium mainly harms domestic and wild birds. Early in the 20th century, it was fashionable to keep parrots as domestic pets. However, many of these birds were affected with ornithosis, leading to sporadic human outbreaks of AC. Hundreds of people died of AC in America, Europe and Africa 1, 2. AC exists in many parts of the world and can infect almost all bird species, including domestic poultry 3. When affected with AC, the mortality rate in infant birds is high, but decreases as birds reach adulthood. Between the 1960’s to 1970’s, the poultry industry in Europe suffered serious losses due to AC 4,5. Not restricted to Europe, AC cases involving duck, dove, chicken, turkey, goose and wild birds have also been reported in China. Indeed a mean positive rate of 10.96% AC has been reported in 18 provinces1. Furthermore, the incidence of AC cases appears to be increasing in some provinces. However, , despite this, no effective vaccine has yet been developed to control the disease. In the current study, specific pathogen free (SPF) chicks were immunized with an avian chlamydial major outer membrane protein (MOMP) gene recombinant adenovirus vector vaccine developed in our laboratory6. The minimal infection dose of the virulent strain, the most effective inoculation route of the vaccine and the minimal effective immunization dose were determined. Vaccine potency, security, protective period, and the conservation period of the vaccine were also examined.
Risk factors for nephrotoxicity associated with continuous vancomycin infusion in outpatient parenteral antibiotic therapy.

OBJECTIVES Continuous vancomycin infusion is increasingly used for outpatient management of infections, but the relationship between vancomycin and nephrotoxicity is controversial. We investigated the risk factors associated with nephrotoxicity in this setting. METHODS A retrospective cohort study of patients receiving continuous vancomycin infusion as outpatient parenteral antibiotic therapy (OPAT) was performed. The likelihood of developing nephrotoxicity (> or =50% increase in serum creatinine from baseline) was evaluated in relation to demographic variables, underlying co-morbidities, infectious disease diagnoses, concomitant drug exposures and vancomycin concentration. Logistic regression was used to determine the association of various variables. Classification and regression tree analysis was used to determine the most significant breakpoint for continuous variables. RESULTS We examined 102 adult patients between January 2004 and June 2007. The mean +/- SD age, baseline serum creatinine and steady-state vancomycin concentration were 48.2 +/- 17.6 years, 78.0 +/- 32.5 micromol/L and 15.5 +/- 10.8 mg/L, respectively. The majority of the patients (66.7%) were treated for bone and joint infection. The cumulative incidence of nephrotoxicity was 15.7%. Nephrotoxicity was found to be associated with hypertension [odds ratio (OR) 5.302 (95% confidence interval (CI) 1.159-24.246), P = 0.031], exposure to aminoglycosides [OR 6.594 (95% CI 1.026-42.385), P = 0.047], loop diuretics [OR 8.123 (95% CI 1.449-45.528), P = 0.017], and steady-state vancomycin concentration > or =28 mg/L [OR 21.236 (95% CI 2.687-167.857), P = 0.004]. CONCLUSIONS We have identified independent risk factors for nephrotoxicity in patients receiving continuous infusion vancomycin in OPAT. A serum steady-state vancomycin concentration > or =28 mg/L markedly increases the risk.
Time it was, and what a time it was...

So much has happened since our January 2010 launch that it's difficult to know even where to begin. While the world of commerce witnessed a catastrophic return to the dark days; the scientific word beheld some of the brightest and most dramatic advances of our time and Bioengineered Bugs was there to chronicle them all.