New embracing approach for better advanced cancer patient comprehensive care.

Introduction: Cancer patients have multiple and complex needs. Argentina has a medium-high cancer incidence. Only 14% of patients with palliative care needs have access to specialized services.

Palliative and prognostic approach in cancer patients identified in the multicentre NECesidades PALiativas 2 study in Argentina.

Background: Early identification of palliative needs has proven benefits in quality of life, survival and decision-making. The NECesidades PALiativas (NECPAL) Centro Coordinador Organización Mundial de la Salud - Instituto Catalán de Oncología (CCOMS-ICO©) tool combines the physician's insight with objective disease progression parameters and advanced chronic conditions. Some parameters have been independently associated with mortality risk in different populations.

Response of factor X deficiency to darutumumab in the treatment of AL amyloidosis: a novel finding.

We report a case of progressive light-chain amyloidosis (otherwise known as AL amyloidosis) with acquired factor X (aFX) deficiency with a complete haematological response and rapid normalisation of FX levels following daratumumab monotherapy. To our knowledge, this is the first case report documenting successful treatment with daratumumab of aFX deficiency secondary to AL amyloidosis. The patient responded well to this therapy, with excellent symptomatic and quality of life improvements as well as a reduction in bleeding manifestations.

Primary aortoduodenal fistula and chronic Q fever infection.

We report a case of chronic Q fever presenting with catastrophic bleeding from an infected abdominal aortic aneurysm causing a primary aortoduodenal fistula in an 80-year-old retired farmer. This presentation is rarely reported in literature and only through case reports. Early diagnosis and definitive surgery were critical to a successful outcome.

A Case of Histoplasmosis with Central Nervous System Relapse after Itraconazole Therapy Needs Further Research.

Central nervous system (CNS) histoplasmosis occurs in 5-20% of all cases and is most commonly seen in immunosuppressed patients who have acquired immunodeficiency syndrome (AIDS) or have received organ transplant. The prevalence of histoplasmosis in patients greater than 65 years old between the years of 1999-2008 in the state of Texas was about 2-3 cases per 100,000 patients year. Since 1990 with the discovery of Triazoles, itraconazole (ICZ) has become the standard initial and suppressive therapy in patients with mild-moderate histoplasmosis without CNS involvement.

Penile melanoma: a 20-Year analysis of six patients at the National Cancer Institute of Peru, Lima.

Unlabelled: Melanoma of the urogenital tract is extremely rare, accounting for less than 0.1% of melanoma cases. The global literature currently describes only 220 cases of penile melanoma, most commonly located on the glans penis.

PEGylated IL-10 Activates Kupffer Cells to Control Hypercholesterolemia.

Interleukin-10 (IL-10) is a multifunctional cytokine that exerts potent context specific immunostimulatory and immunosuppressive effects. We have investigated the mechanism by which PEGylated rIL-10 regulates plasma cholesterol in mice and humans. In agreement with previous work on rIL-10, we report that PEGylated rIL-10 harnesses the myeloid immune system to control total plasma cholesterol levels.

The Potentiation of IFN-γ and Induction of Cytotoxic Proteins by Pegylated IL-10 in Human CD8 T Cells.

Interleukin-10 (IL-10) exerts both immunosuppressive and immunostimulatory effects. While the immunosuppressive effects are widely known, it has only been recently reported that pegylated recombinant human IL-10 (PEG-rHuIL-10) elicits potent interferon-γ (IFN-γ) and CD8 T-cell-dependent antitumor effects in murine tumor models. In this study, we show that PEG-rHuIL-10 exerts immune inhibitory effects on human peripheral blood mononuclear cell (PBMC) bulk cultures and stimulatory effects in CD8 T cells within the same culture.

Impact of previous pharmacy work experience on pharmacy school academic performance.

Objectives: To determine whether students' previous pharmacy-related work experience was associated with their pharmacy school performance (academic and clinical).

Methods: The following measures of student academic performance were examined: pharmacy grade point average (GPA), scores on cumulative high-stakes examinations, and advanced pharmacy practice experience (APPE) grades. The quantity and type of pharmacy-related work experience each student performed prior to matriculation was solicited through a student survey instrument.

Application of proteomics methods for pathogen discovery.

Proteomics have been used widely to study proteins in complex materials such as cells, body fluids, tissues, and organisms. Application of advance proteomic techniques for the characterization of disease-specific proteins may provide information for the detection of potential infectious agents. In this report, two proteomics techniques, a two-dimensional differential gel electrophoresis (2D-DIGE) and a one-dimensional gel electrophoresis and one-dimensional liquid chromatography coupled with mass spectrometry (GeLC-MS/MS), were applied for investigating viral proteins from cultured cells inoculated with a clinical sample.

A surface on the androgen receptor that allosterically regulates coactivator binding.

Current approaches to inhibit nuclear receptor (NR) activity target the hormone binding pocket but face limitations. We have proposed that inhibitors, which bind to nuclear receptor surfaces that mediate assembly of the receptor's binding partners, might overcome some of these limitations. The androgen receptor (AR) plays a central role in prostate cancer, but conventional inhibitors lose effectiveness as cancer treatments because anti-androgen resistance usually develops.

Structural insight into the mode of action of a direct inhibitor of coregulator binding to the thyroid hormone receptor.

The development of nuclear hormone receptor antagonists that directly inhibit the association of the receptor with its essential coactivators would allow useful manipulation of nuclear hormone receptor signaling. We previously identified 3-(dibutylamino)-1-(4-hexylphenyl)-propan-1-one (DHPPA), an aromatic beta-amino ketone that inhibits coactivator recruitment to thyroid hormone receptor beta (TRbeta), in a high-throughput screen. Initial evidence suggested that the aromatic beta-enone 1-(4-hexylphenyl)-prop-2-en-1-one (HPPE), which alkylates a specific cysteine residue on the TRbeta surface, is liberated from DHPPA.

Discovery of small molecule inhibitors of the interaction of the thyroid hormone receptor with transcriptional coregulators.

Thyroid hormone (3,5,3'-triiodo-L-thyronine, T3) is an endocrine hormone that exerts homeostatic regulation of basal metabolic rate, heart rate and contractility, fat deposition, and other phenomena (1, 2). T3 binds to the thyroid hormone receptors (TRs) and controls their regulation of transcription of target genes. The binding of TRs to thyroid hormone induces a conformational change in TRs that regulates the composition of the transcriptional regulatory complex.

The molecular mechanisms of coactivator utilization in ligand-dependent transactivation by the androgen receptor.

Androgens drive sex differentiation, bone and muscle development, and promote growth of hormone-dependent cancers by binding the nuclear androgen receptor (AR), which recruits coactivators to responsive genes. Most nuclear receptors recruit steroid receptor coactivators (SRCs) to their ligand binding domain (LBD) using a leucine-rich motif (LXXLL). AR is believed to recruit unique coactivators to its LBD using an aromatic-rich motif (FXXLF) while recruiting SRCs to its N-terminal domain (NTD) through an alternate mechanism.

Glycoproteins M and N of human herpesvirus 8 form a complex and inhibit cell fusion.

Glycoproteins M (gM) and N (gN) are well conserved across the herpesvirus family and their involvement in virus penetration and egress is well described, especially for alphaherpesviruses. Because there was no previous study on the homologues of human herpesvirus 8 glycoproteins M (gM8) and N (gN8), we analysed their biochemical and functional characteristics. We found that: (i) gM8 aggregated following heat treatment; (ii) gM8 was a virion component; (iii) gM8 and gN8 were N-glycosylated; (iv) gM8 formed a specific complex with gN8; and (v) gN8 was required for functional processing of gM8.

Comparison of serologic assays for detection of antibodies against human herpesvirus 8.

Improvement of serologic assays for detection of antibodies against human herpesvirus 8 (HHV-8) is critical to better understand its epidemiology and biology. We produced the HHV-8 latent (ORF73) and lytic (ORF65, K8.1, and glycoprotein B) antigens in the Semliki Forest virus system and evaluated their performance in immunofluorescence assays (IFAs) and enzyme-linked immunosorbent assays (ELISAs).

Characterization of a novel D1S80 pseudoallele.

During a D1S80 population study conducted for databasing purposes in the New York City Ashkenazi Jewish population, eight out of 96 samples were typed with a band corresponding to the position of a #15 allele. In seven of the eight samples, three bands appeared. Further investigation was needed to explain the high frequency of an allele considered so rare that it is not included in the commercially provided allelic ladder.

New immunofluorescence assays for detection of Human herpesvirus 8-specific antibodies.

Several assays have been developed for detection of immunoglobulin G antibodies to Human herpesvirus 8 (HHV-8), including immunofluorescence assays (IFAs) and enzyme-linked immunosorbent assays (ELISAs). However, the specificity and sensitivity of these assays are not completely defined due to the lack of a "gold standard." Although IFAs based on primary effusion lymphoma (PEL) cell lines are used widely, the assays can be confounded by nonspecific reactions against cellular components and potential cross-reaction with antibodies against other herpesviruses.

D1S80 allele frequencies in Hasidic and non-Hasidic New York City Jewish populations.

Allele frequencies were determined for the VNTR locus D1S80 in Hasidic and non-Hasidic Ashkenazi New York City Jewish subpopulations. Samples were amplified via the polymerase chain reaction and underwent genotyping using polyacrylamide gel electrophoresis. In the Hasidic population 14 alleles were observed as opposed to 19 alleles in the non-Hasidic community.

Antioxidant-sensitive regulation of inflammatory-response genes in Kaposi's sarcoma cells.

Kaposi's sarcoma (KS) is a multifocal vascular lesion characterized by abnormal proliferation of endothelial-like KS cells linked to a pronounced leukocyte infiltration. KS lesions contain novel herpes-like DNA sequences, KSHV, hypothesized to originate from the viral pathogen for KS. Using cultured KS cells that retain the KSHV sequences, diverse signals, including tumor necrosis factor alpha, interleukin (IL) 1 beta, polyinosinic acid/polycytidylic acid and lipopolysaccharide, induced the expression of the cytokine IL-6 and cellular adhesion molecules involved in leukocyte recruitment, including vascular adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1).

The prevalence of lumbar paraspinal spontaneous activity in asymptomatic subjects.

Electrodiagnostic findings of fibrillations and positive sharp waves in the lumbosacral paraspinals in patients without previous back surgery has been generally considered to be abnormal, consistent with posterior rami denervation. In some cases, it is the only abnormality on the electromyographic examination. This study was undertaken to determine the prevalence of abnormal spontaneous activity in lumbosacral paraspinals in asymptomatic individuals.

Is Kaposi's-sarcoma-associated herpesvirus detectable in semen of HIV-infected homosexual men?

We explored a possible route of transmission of Kaposi's-sarcoma-associated herpes virus (KSHV) with nested and unnested PCR techniques. We looked for KSHV DNA sequences in semen of HIV-positive homosexual men and HIV-negative healthy semen donors. With unnested primers we found KSHV sequences in 21 of 33 (64%) homosexual men and in none of 30 healthy donors.

Some nucleoside analogs with anti-human immunodeficiency virus activity inhibit replication of Epstein-Barr virus.

The effects of (+)-beta-D-dioxolane-cytosine ((+)-D-beta-DOC), (-)-beta-L-dioxolane-cytosine ((-)-L-beta-DOC), (+)-beta-D-oxathiolane-cytosine ((+)-D-beta-OTC), (-)-beta-L-oxathiolane-cytosine ((-)-L-beta-OTC, or 3TC), 3'-azido-2',3'-dideoxy-5-methyl-cytidine (5-Me-AZDC), and 3'-azido-2',3'-dideoxyuridine (AZDU) on Epstein-Barr virus (EBV) DNA replication in vitro were tested in P3HR-1 cells. Two anti-EBV drugs, 3'-azido-3'-deoxythymidine (AZT) and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG, or ganciclovir), were used as positive controls. The inhibitory effects on EBV DNA synthesis were quantified by membrane filter and Southern blot hybridizations with an EBV-specific probe BamHI-W fragment.