Psychological distress as predictor of quality of life in men experiencing infertility: a cross-sectional survey

Background  

Infertility is associated with impairment in human life. The quality of life (QOL) construct allows measuring the impact of health conditions in a broader way. The study aimed to explore the impact of the psychological distress on QOL's dimensions in men experiencing infertility.     

Neonatal phencyclidine administration and post-weaning social isolation as a dual-hit model of ‘schizophrenia-like’ behaviour in the rat

Rationale

Schizophrenia is a debilitating disorder comprising positive, negative and cognitive deficits with a poorly defined neurobiological aetiology; therefore, animal models with greater translational reliability are essential to develop improved therapies.

Objectives

This study combines two developmental challenges in rats, neonatal phencyclidine (PCP) injection and subsequent rearing in social isolation from weaning, to attempt to produce more robust behavioural deficits with greater translational relevance to schizophrenia than either challenge alone.

Methods

Forty-two male Lister-hooded rat pups received the N-methyl-d-aspartate (NMDA) receptor antagonist, phencyclidine (PCP, 10 mg/kg, s.c.), or vehicle on post-natal day (PND) 7, 9 and 11 and were weaned on PND 23 into group housing (saline-treated n?=?11 or PCP-treated n?=?10) or isolation (saline n?=?10 or PCP n?=?11). Six weeks post-weaning, novelty- and PCP-induced (3.2 mg/kg) locomotor activity, novel object discrimination, prepulse inhibition of acoustic startle and contextual memory in a conditioned emotion response (CER) were recorded.

Results

Isolation rearing alone significantly elevated baseline locomotor activity and induced visual recognition memory impairment in novel object discrimination. Neonatal PCP treatment did not induce locomotor sensitisation to a subsequent acute PCP injection, but it impaired prepulse inhibition when combined with isolation rearing. CER freezing behaviour was significantly reduced by isolation rearing but an even greater effect occurred when combined with neonatal PCP treatment.

Conclusions

Neonatal PCP and isolation rearing both produce behavioural deficits in adult rats, but combined treatment caused a wider range of more severe cognitive impairments, providing a more comprehensive preclinical model to determine the neurobiological aetiology of schizophrenia than either treatment alone.     

Mixed hematopoietic chimerism following bone marrow transplantation for hematologic malignancies

Twenty-nine of 172 patients (17%) who received an allogeneic bone marrow transplant (BMT) from histocompatible sibling donors for hematologic malignancies were mixed hematopoietic chimeras; ie, they had a mixture of donor and host hematopoietic or lymphohematopoietic cells at greater than or equal to 14 days after transplantation. Twenty- four of the 29 mixed chimeras (83%) have remained in continuous complete remission for up to 116 months (greater than 9 years) following BMT. Four of the 29 patients (14%) have had recurrent leukemia, and 7 of the 29 (24%) have had moderate or severe graft-v- host disease (GVHD). Twelve of these 29 patients have persisted as stable mixed chimeras for greater than or equal to 2 years after BMT, whereas other patients converted to all donor-type hematopoiesis. The incidence of mixed chimerism was independent of the pretransplant regimen, the donor or recipient age (less than 20 v greater than 20 years), remission status (first complete remission of acute leukemia and first chronic phase of chronic myelocytic leukemia v later stages of disease), and type of leukemia. Our data indicate that mixed hematopoietic chimerism is not rare after BMT for hematologic malignancies and that its presence is compatible with long-term disease- free survival. Prospective studies of mixed chimerism after BMT are warranted to achieve better understanding of its biologic importance.     

Cytosolic free calcium levels in sickle red blood cells

In this study, we used a recently developed nuclear magnetic resonance (NMR) technique to measure ionized calcium in sickle erythrocytes. The NMR technique, which involves 19F NMR studies of a fluorinated calcium chelator quinMF, [2-(2-amino-4-methyl-5-fluorophenoxy)methyl-8- aminoquinoline-N,N,N',N'- tetraacetic acid] provides a novel approach to the study of ionized calcium in erythrocytes since the presence of hemoglobin precludes the use of fluorescent calcium indicators. The mean value for ionized calcium in oxygenated sickle erythrocytes was 18 +/- 2 nmol/L (SE). Experiments with normal RBCs gave a mean value of 21 +/- 2 nmol/L (SE). After 1 hour of deoxygenation, mean values for ionized calcium in sickle erythrocytes did not increase as compared with values obtained under oxygen. To investigate whether deoxygenation stimulated endocytosis, sickle erythrocytes were deoxygenated for 1 hour in the presence of impermeant FBAPTA (1,2 bis-(2-amino-5- fluorophenoxy) ethane N,N,N',N'-tetraacetic acid). Cells were then separated from the extracellular medium and assayed for the presence of FBAPTA; they had incorporated significant quantities of the extracellular FBAPTA. This incorporation was not observed with normal erythrocytes. These data are consistent with at least a portion of the elevation in total cell calcium in sickle erythrocytes arising as a consequence of an endocytotic process in which extracellular calcium ions are incorporated into vesicles. Additional experiments show that these intracellular vesicles accumulate Ca2+ on further deoxygenation, consistent with a transient increase in ionized cell calcium. These studies represent the first use of NMR spectroscopy to evaluate endocytotic processes.     

Mechanism of differential inhibition of factor-dependent cell proliferation by transforming growth factor-beta 1: selective uncoupling of FMS from MYC

Transforming growth factor-beta 1 (TGF-beta 1) selectively modulates hematopoietic cell proliferation. The proliferation of FDC-P1 clone MAC- 11, a factor-dependent murine myeloid progenitor cell line, was inhibited differentially by TGF-beta 1: strongly in macrophage colony- stimulating factor (M-CSF), mildly in interleukin-3, and not at all in granulocyte-macrophage-CSF (GM-CSF). Flow cytometry and Western blots showed an unexpected increase in expression of FMS, the receptor for M- CSF, in response to TGF-beta 1. Metabolic labeling with 35S-methionine showed that synthesis of FMS protein accelerated in response to TGF- beta 1, whereas its degradation was unaffected. Northern analyses showed a rapid increase in c-fms RNA after the addition of TGF-beta 1. TGF-beta 1 did not affect kinase activity, cellular phosphotyrosine response, or internalization of FMS. However, TGF-beta 1 inhibited the induction by M-CSF of c-myc RNA analyzed on Northern blots and protein detected by radioimmuno-precipitation. TGF-beta 1 did not affect induction of c-myc expression by GM-CSF or induction of c-fos or c-jun by M-CSF. Therefore, FMS and the GM-CSF receptor induce c-myc via signal transduction pathways that differ in that only the former is inhibited by TGF-beta 1. This inhibition may account for the selective growth regulation by TGF-beta 1.     

Indeterminate mediastinal invasion in bronchogenic carcinoma: CT evaluation

The computed tomographic (CT) scans of 80 patients with bronchogenic carcinoma classified as indeterminate for direct mediastinal invasion were retrospectively reviewed after the patients had undergone thoracotomy. Forty-eight (60%) of the masses were resectable, without invasion of the mediastinum, 18 (22%) focally invaded the mediastinum but were technically resectable, and 14 (18%) invaded the mediastinum and were not technically resectable. Although in most circumstances in this relatively small subset of patients CT was not helpful in differentiating masses with and without mediastinal invasion, CT was able to separate a large group of masses that were likely to be technically resectable. Thirty-six (97%) of 37 masses with one or more of these CT findings were considered technically resectable: contact of 3 cm or less with mediastinum, less than 90 degrees of contact with aorta, and mediastinal fat between mass and mediastinal structures. Of these 36 masses, 28 were resectable without mediastinal invasion, and eight were resectable with focal limited mediastinal invasion.