Final analysis of the ALTTO trial: adjuvant trastuzumab in sequence or in combination with lapatinib in patients with HER2-positive early breast cancer [BIG 2-06/NCCTG N063D (Alliance)].

Background: Dual anti-human epidermal growth factor receptor 2 (HER2) blockade has improved the outcomes of patients with early and metastatic HER2-positive breast cancer. Here we present the final 10-year analysis of the ALTTO trial.

Patients And Methods: The ALTTO trial (NCT00490139) is a prospective randomized, phase III, open-label, multicenter study that investigated the role of adjuvant chemotherapy and trastuzumab alone, in combination or sequentially with lapatinib.

[Not Available].

Adjuvant and neoadjuvant therapy of early breast cancer reduces the risk of relapse and breast cancer mortality. Treatment modalities include chemotherapy, endocrine therapy, human epidermal growth factor receptor 2-targeted agents, bisphosphonates, immunotherapy, cyclin-dependent kinase inhibitors 4/6- and poly-ADP-ribose polymerase inhibitors. All cases are reviewed at multidisciplinary breast cancer tumour boards.

[Not Available].

Metastatic breast cancer claims the lives of 1,000 Danish women each year. Current guidelines are focused on the three major immunohistochemical subtypes in breast cancer. This review covers current Danish guidelines for the treatment of advanced breast cancer and highlights the potential future treatments for Danish patients.

The impact of erythropoiesis-stimulating agents administration concomitantly with adjuvant anti-HER2 treatments on the outcomes of patients with early breast cancer: a sub-analysis of the ALTTO study.

Purpose: To assess whether erythropoiesis-stimulating agents (ESA) administration impacts the outcomes of patients with HER2-positive early breast cancer (EBC).

Methods: ALTTO (NCT00490139) patients were categorized by ESA use during adjuvant anti-HER2 treatment. Disease-free-survival (DFS), overall survival (OS), and time-to-distant recurrence (TTDR) were analyzed by ESA administration, with subgroup analyses according to prognostic factors.

Greater maltreatment severity is associated with smaller brain volume with implication for intellectual ability in young children.

Background: Childhood maltreatment profoundly alters trajectories of brain development, promoting markedly increased long-term health risks and impaired intellectual development. However, the immediate impact of maltreatment on brain development in children and the extent to which altered global brain volume contributes to intellectual development in children with maltreatment experience is currently unknown. We here utilized MRI data obtained from children within 6 months after the exposure to maltreatment to assess the association of maltreatment severity with global brain volume changes.

Aromatase Inhibitor-Related Symptoms Reported by Postmenopausal Women with Nonmetastatic, Estrogen Receptor-Positive Breast Cancer: A Systematic Review.

Purpose: The objective of this systematic review was to establish an overview of aromatase inhibitor-related symptoms reported by postmenopausal women with nonmetastatic, estrogen receptor-positive breast cancer.

Data Sources: Eight databases (PubMed, Cochrane, Cumulative Index to Nursing and Allied Health Literature [CINAHL], Ovid EMBASE, Ovid MEDLINE, PsycINFO, Scopus, and Web of Science) were searched for trials published between January 2004 and November 2021. Inclusion criteria were studies exploring patient-reported aromatase inhibitor-related symptoms in postmenopausal women with nonmetastatic estrogen receptor-positive breast cancer.

Immediate impact of child maltreatment on mental, developmental, and physical health trajectories.

Objective: The immediate impact of child maltreatment on health and developmental trajectories over time is unknown. Longitudinal studies starting in the direct aftermath of exposure with repeated follow-up are needed.

Method: We assessed health and developmental outcomes in 6-month intervals over 2 years in 173 children, aged 3-5 years at study entry, including 86 children with exposure to emotional and physical abuse or neglect within 6 months and 87 nonmaltreated children.

Sensory-Tactile Functional Mapping and Use-Associated Structural Variation of the Human Female Genital Representation Field.

The precise location of the human female genital representation field in the primary somatosensory cortex (S1) is controversial and its capacity for use-associated structural variation as a function of sexual behavior remains unknown. We used a functional magnetic resonance imaging (fMRI)-compatible sensory-tactile stimulation paradigm to functionally map the location of the female genital representation field in 20 adult women. Neural response to tactile stimulation of the clitoral region (vs right hand) identified individually-diverse focal bilateral activations in dorsolateral areas of S1 (BA1-BA3) in alignment with anatomic location.

Childhood adversity correlates with stable changes in DNA methylation trajectories in children and converges with epigenetic signatures of prenatal stress.

Childhood maltreatment (CM) is an established major risk factor for a number of negative health outcomes later in life. While epigenetic mechanisms, such as DNA methylation (DNAm), have been proposed as a means of embedding this environmental risk factor, little is known about its timing and trajectory, especially in very young children. It is also not clear whether additional environmental adversities, often experienced by these children, converge on similar DNAm changes.

Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry.

Microglia, the specialized innate immune cells of the CNS, play crucial roles in neural development and function. Different phenotypes and functions have been ascribed to rodent microglia, but little is known about human microglia (huMG) heterogeneity. Difficulties in procuring huMG and their susceptibility to cryopreservation damage have limited large-scale studies.

[Early detection and treatment of breast cancer].

Breast cancer is the most common cancer among Danish women. In Denmark, mammography screening has been implemented since 2010. The surgical approach has turned from mastectomy and axillary clearance to breast conserving surgery and sentinel node procedure.

Expression Patterns of Biomarkers in Primary Tumors and Corresponding Metastases in Breast Cancer.

Tumor heterogeneity has been shown for several cancers including breast cancer (BC). Despite the fact that expression of tumor markers may change throughout the metastatic process, rebiopsies at the time of recurrence are still not performed routinely at all institutions. The aims of the study were to evaluate changes in biomarker profiles during the metastatic process and to investigate whether previous anthracycline or endocrine therapy given in the adjuvant setting could affect the biomarker profile in metastatic lesions.

T-lymphocyte perturbation following large-scale apheresis and hematopoietic stem cell transplantation in HIV-infected individuals.

Analysis and mathematical modeling of T-lymphocyte perturbation following administration of granulocyte colony stimulating factor (G-CSF) and two large-scale aphereses are reported. 74 HIV-1 positive antiretroviral-treated individuals were infused with gene- or sham-transduced CD34+ hematopoietic stem cells (HSC) in a Phase II clinical trial. T cell numbers were examined in four phases: 1) during steady state; 2) increases in peripheral blood (PB) following G-CSF administration; 3) depletion post-aphereses and 4) reconstitution post HSC infusion.

Allele frequencies of 11 X-chromosomal loci of two population samples from Africa.

Eleven X-chromosomal STRs from two multiplex PCR approaches (DXS6807, DXS8378, DXS7132, DXS6800, DXS9898, DXS7424, DXS101, DXS7133, HPRTB, DXS8377, and DXS7423), located in four different X-chromosomal linkage groups, were typed in two population samples from Africa, Morocco, and Madagascar. Forensic efficiency parameters such as polymorphism information content and mean exclusion chance were calculated. A deviation from the Hardy–Weinberg equilibrium could not be found.

Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells.

Gene transfer has potential as a once-only treatment that reduces viral load, preserves the immune system and avoids lifetime highly active antiretroviral therapy. This study, which is to our knowledge the first randomized, double-blind, placebo-controlled, phase 2 cell-delivered gene transfer clinical trial, was conducted in 74 HIV-1-infected adults who received a tat-vpr-specific anti-HIV ribozyme (OZ1) or placebo delivered in autologous CD34+ hematopoietic progenitor cells. There were no OZ1-related adverse events.

Compacted artificially cemented soil-acid leachate contaminant interactions: breakthrough curves and transport parameters.

The transport of contaminants through compacted artificially cemented soil subjected to acid leachate contaminant percolation was analyzed by means of laboratory column tests. The effect of cement content, degree of acidity and hydraulic gradient were evaluated after permeation of several pore volumes of acid leachate contaminant flow through the soil. The pH, electric conductivity and solute breakthrough curves were considered throughout the study.

Long-term survival and concomitant gene expression of ribozyme-transduced CD4+ T-lymphocytes in HIV-infected patients.

Background: An anti-HIV-1 tat ribozyme, termed Rz2, has been shown to inhibit HIV-1 infection/replication and to decrease HIV-1-induced pathogenicity in T-lymphocyte cell lines and normal peripheral blood T-lymphocytes. We report here the results of a phase I gene transfer clinical trial using Rz2.

Methods: Apheresis was used to obtain a peripheral blood cell population from each of four HIV-negative donors.

Artificial capillary culture: expansion and retroviral transduction of CD4+ T-lymphocytes for clinical application.

An artificial capillary culture/transduction technique has been developed for application in a phase I gene therapy clinical trial for HIV. The trial protocol involves isolation of CD4+ T-lymphocytes from a genetically matched HIV negative twin, retroviral transduction of equal numbers of cells with the ribozyme therapeutic and control genes, and expansion in Cellmax artificial capillary modules. Preclinical studies showed transduction efficiencies in the range of 3-30%, with preferential expansion of CD4+ lymphocytes over a culture period of 10-14 days.

[The epidemiology and epizootiology of rabies on the territory of the former USSR].

On the territory of the former USSR rabies is as infection with natural foci in the western and central regions. In the republics of Central Asia and Transcaucasia, in the North Caucasus the presence of natural foci of infection is combined with appearance of the foci of rabies, mainly among dogs, due to human activities. The existence of natural epizootic cycles of three years has been established, and the natural foci of rabies have been found to prevail in certain landscape zones: steppes, forest-steppes, tundra, forest tundra.

Sulfated polysaccharides are required for collagen-induced vascular tube formation.

We have previously shown that soluble type I collagen can induce vascular tube formation when it contacts the apical side of a confluent endothelial monolayer. In this study we have examined which soluble agent(s) are required for collagen-induced tube formation. Human neonatal foreskin microvascular endothelial cells, maintained in basal medium, were preincubated with each test agent for 2 h prior to the addition of solubilised type I collagen (100 micrograms/ml).

VLA-2 mediates the interaction of collagen with endothelium during in vitro vascular tube formation.

A confluent endothelial monolayer can be induced to form vascular tubes in response to collagen. We investigated possible mechanisms of collagen-induced tube formation by using antibodies to the VLA-2 integrin receptor and protein kinase C inhibitors. Pre-incubation of cells with anti-VLA-2 (which recognises both the alpha 2 and beta 1 chains) and AK7 (which recognises only the alpha 2 chain) showed a dose-dependent inhibition of tube formation.

Production of an early release, M(r) 36,000 monokine by stimulated rat macrophages.

Supernatants from rat peritoneal macrophage cultures stimulated with bacterial products contain a M(r) 36,000 factor that protects immature cortical thymocytes from loss of viability over a 4-hr incubation period in vitro. This effect could not be produced with purified transforming growth factor-beta or recombinant interleukin-6 (IL-6). Further, the partially purified M(r) 36,000 fraction was inactive in bioassays for IL-1 and tumour necrosis factor.

[Postinfection and postvaccinal antianthrax immunity in human subjects].

Antibodies to Bacillus anthracis protective antigen (PA) and to the lethal factor (LF) of B. anthracis exotoxin in the blood sera of anthrax patients and of subjects with a history of the disease, as well as of persons immunized with STI live vaccine, were studied by the heterogeneous enzyme immunoassay. In 1-6 years after convalescence the levels of anti-PA and anti-LF antibodies (at 75% and 96% detection rates respectively) were higher than on weeks 1-4 from the onset of the disease.