Mortality among patients with pulmonary non-tuberculous mycobacteria disease.

SETTING: Tertiary referral center, National Institutes of Health (NIH), USA. OBJECTIVE: To estimate the mortality rate and its correlates among persons with pulmonary non-tuberculous mycobacteria (PNTM) disease. DESIGN: A retrospective review of 106 patients who were treated at the NIH Clinical Center and met American Thoracic Society/Infectious Diseases Society of America criteria for PNTM. Eligible patients were aged ⩾18 years and did not have cystic fibrosis or human immunodeficiency virus (HIV) infection. RESULTS: Of 106 patients followed for a median of 4.9 years, 27 (25%) died during follow-up, for a mortality rate of 4.2 per 100 person-years. The population was predominantly female (88%) and White (88%), with infrequent comorbidities. Fibrocavitary disease (adjusted hazard ratio [aHR] 3.3, 95% confidence interval [CI] 1.3-8.3) and pulmonary hypertension (aHR 2.1, 95%CI 0.9-5.1) were associated with a significantly elevated risk of mortality in survival analysis. CONCLUSIONS: PNTM remains a serious public health concern, with a consistently elevated mortality rate across multiple populations. Significant risk factors for death include fibrocavitary disease and pulmonary hypertension. Further research is needed to more specifically identify clinical and microbiologic factors that jointly influence disease outcome.

Assessment of diffraction-enhanced synchrotron imaging for cartilage degeneration of the human knee joint.

Diffraction-enhanced imaging (DEI) is a radiographic technology that harnesses the X-ray refraction and scatter rejection properties that are not available with conventional radiography. Here, we test the efficacy of planar DEI to render images from which cartilage degeneration, characteristic of osteoarthritis, can be detected. DEI was carried out on human cadaveric intact knee joints at the X-15 beamline at the National Synchrotron Light Source. The gross specimens and the DEI images were graded separately for levels of cartilage degeneration on six individual surfaces: anterior and posterior femoral and tibial on both medial and lateral sides. There was a significant correlation between the actual levels of cartilage degeneration and what was observed in their respective DEI images (P < 0.05) for all six articular surfaces. Some articular surfaces (patellar surfaces, in particular) could not be visualized because of overlap with superimposed bone. Sensitivity for the graded articular surfaces was 0.73 and specificity was 0.92 (Grade 0 being no lesion and Grades 1-6 being increasing gradations of lesions). Chondrocalcinosis was also observed in DEI images to a far greater extent compared with the conventional radiographs. DEI renders images that are significantly correlated with their actual gross morphology. Detection of lesions was better for more severe grades of degeneration than for partial focal lesions. Although some articular surfaces could not be visualized because of superimposed bone, we feel that DEI has potential for the diagnosis of cartilage lesions and chondrocalcinosis.

Depressive symptoms in schizophrenic patients.

Distinction between true negative and depressive symptoms in schizophrenia is difficult. In the present study we seek to establish the psychological profile of depression-prone schizophrenic patients. We addressed the issue by comparing the expression of psychological indices, such as the feelings of being in control of events, anxiety, mood, and the style of coping with stress in depressive and non-depressive schizophrenics. We also analyzed the strength of the association of these indices with the presence of depressive symptoms. A total of 49 patients (18 women and 31 men, aged 23-59) were enrolled into the study, consisting of a self-reported psychometric survey. We found that the prevalence of clinically significant depression in schizophrenic patients was 61%. The factors which contributed to the intensification of depressive symptoms were the external locus of control, anxiety, gloomy mood, and the emotion-oriented coping with stress. We conclude that psychological testing may discern those schizophrenic patients who would be at risk of depression development and may help separate the blurred boundaries between depressive and negative symptoms of schizophrenia.

Personality and perception of stigma in psychiatric patients with depressive disorders.

OBJECTIVE: The study seeks to determine the relationships between neuroticism and extroversion, on the one side, and the perception of various dimensions of social stigma, on the other, in psychiatric in-patients with depressive disorders, such as depressive episodes, or mood and anxiety disorders with the presence of depressive symptoms. MATERIAL AND METHODS: A total of 72 patients were examined in the study. Twenty four of them (F/M - 12/12; age range 42-65 years) were used for assessing the reliability of a depression stigma questionnaire (DSQ) created specifically for this study. The remaining 48 patients (F/M - 31/17; age range 17-74 years) were then surveyed with the DSQ and other psychometric tools employed in the study. Self-reported data on the self-stigma, perceived stigma, public (mirrored) stigma, secrecy, treatment stigma, and the levels of neuroticism, extroversion, and depression were collected. RESULTS: The study demonstrates that treatment stigma and secrecy were the most frequent aspects of stigma experienced by the patients. Secrecy correlated negatively with age and positively with the education level. There were correlations between neuroticism and four of the stigma dimensions: treatment stigma, secrecy, perceived stigma, and self-stigma. Extroversion, in turn, correlated with perceived stigma, public stigma, and self-stigma. CONCLUSIONS: The study confirms the relevance of personality resources in the perception and coping with stigma and points to secrecy as a major underlying factor in these processes. In light of the present findings, stigma experienced by the patient is not only related to the external indicators of social stigmatization and the state of depression, but also to the personal features of an individual.

Neosartorya udagawae (Aspergillus udagawae), an emerging agent of aspergillosis: how different is it from Aspergillus fumigatus?

A recent report on several cases of invasive aspergillosis caused by Neosartorya udagawae suggested distinctive patterns of disease progression between N. udagawae and Aspergillus fumigatus. This prompted us to characterize N. udagawae in comparison to A. fumigatus. Our findings showed that both species exist in two mating types at similar ratios and produce gliotoxin. However, the thermotolerance of the two species differs: while A. fumigatus is able to grow at 55 degrees C but not at 10 degrees C, N. udagawae is able to grow at 10 degrees C but fails to grow at >42 degrees C. Furthermore, compared to A. fumigatus, the conidia of N. udagawae require longer incubation periods to germinate at 37 degrees C and are more susceptible to neutrophil attack as well as hydrogen peroxide; N. udagawae is also less virulent in gp91(phox-/-) mice. These findings suggest that growth and susceptibility to the host response might account for the reduced virulence of N. udagawae and the subtle distinction in the progression of the disease caused by the two species.

Mass antibiotic treatment to stop an outbreak of meningococcal disease: a molecular analysis.

The occurrence of three cases of meningococcal disease among children in a small community, two of whom attended the same day-care centre, prompted a programme of mass antibiotic prophylaxis. Nasopharyngeal and throat swabs were obtained on three occasions from all children registered at the day-care centre. Serogroup B Neisseria meningitidis was isolated from 13 of 61 children before prophylaxis, from three children after 2 weeks, and from 19 children after 3 months. Repetitive extragenic palindromic PCR analysis identified several meningococcal strains before treatment, one of which became predominant after 3 months. Mass antibiotic prophylaxis initially suppressed meningococcal carriage, but the carriage rate subsequently rebounded.

The NG domain of the prokaryotic signal recognition particle receptor, FtsY, is fully functional when fused to an unrelated integral membrane polypeptide.

Recent studies have revealed that Escherichia coli possesses an essential targeting system for integral membrane proteins, similar to the mammalian signal recognition particle (SRP) machinery. One essential protein in this system is FtsY, a homologue of the alpha-subunit of the mammalian SRP-receptor (SR-alpha). However, E. coli does not possess a close homologue of the integral membrane protein SR-beta, which anchors SR-alpha to the membrane. Moreover, although FtsY can be found as a peripheral membrane protein, the majority is found soluble in the cytoplasm. In this study, we obtained genetic and biochemical evidence that FtsY must be targeted to the membrane for proper function. We demonstrate that the essential membrane targeting activity of FtsY is mediated by a 198-residue-long acidic N-terminal domain. This domain can be functionally replaced by unrelated integral membrane polypeptides, thus avoiding the need for specific FtsY membrane targeting factors. Therefore, the N terminus of FtsY constitutes an independent domain, which is required only for the targeting of the C-terminal NG domain of FtsY to the membrane.

Quantitative analysis of the plain radiographic appearance of Ewing's sarcoma of bone.

RATIONALE AND OBJECTIVES: The authors quantitate the radiographic features that distinguish the plain radiographic appearance of Ewing's sarcoma (ES) from other solitary lesions of bone. METHODS: A total of 709 cases of focal bone lesions, including 44 ES, were analyzed according to demographic, anatomic, and plain radiographic features. Vector analysis of groups of features was performed to determine those that are most sensitive and specific for the appearance of ES in contrast with other lesions in the database. RESULTS: In our sample, Ewing's sarcoma is most consistently a medullary-based (91%) lytic (89%) lesion with at least a partially permeative appearance (82%), poorly defined edges (82%), no margination (91%), and a soft-tissue mass (61%). When these lesions occur in long bones, they most commonly are found in the diaphysis (75%) and are proximal more often than distal. Vector analysis suggests that any primary bone lesion without radiographically visible matrix and with either a soft-tissue mass, an appearance of permeative destruction alone or in combination with other patterns of bone destruction is suspect for the diagnosis. This small subset of common features appears to have a high sensitivity (89%) and prevalence (47%) of ES among the lesions meeting these criteria. Limiting the age of the patients to progressively younger age groups increases the specificity but lowers sensitivity. The vector analysis-generated differential diagnoses includes osteosarcoma, giant-cell tumor, lymphoma, and chondrosarcoma. CONCLUSIONS: A relatively specific set of radiographic features can be defined, which will assist in the radiographic diagnosis of ES and improve upon current textbook descriptions.

Biogenesis and topology of integral membrane proteins: characterization of lactose permease-chloramphenicol acetyltransferase hybrids.

Use of beta-lactamase in gene fusions to study membrane protein topology permits exploitation of its biological activity to select for positive (external) hybrids on ampicillin agar plates. When the enzyme is attached to cytoplasmic loops of a membrane protein, it is not secreted and is therefore unable to confer ampicillin resistance. In this study, we examine the use of the cytoplasmic enzyme chloramphenicol acetyltransferase (Cat) as a complement to the use of periplasmic beta-lactamase, in gene fusion studies. This enzyme is responsible for chloramphenicol resistance in Escherichia coli. We show that Cat confers substantial antibiotic resistance when fused to cytoplasmic loops of lactose permease. As expected, periplasmically exposed Cat is enzymatically active in vitro but unable to confer significant chloramphenicol resistance, presumably because of the absence of acetylcoenzyme A in the periplasm. Therefore, Cat may serve as a topogenic sensor in gene fusion studies. The new Cat fusion approach is discussed with regard to its potential use for selecting E. coli mutants which are defective in the assembly of membrane proteins.

Plasma Membrane Sterols Are Essential for Sensing Osmotic Changes in the Halotolerant Alga Dunaliella.

The halotolerant alga Dunaliella responds to hyperosmotic stress by synthesis of massive amounts of glycerol. The trigger for this osmotic response is the change in cell volume, but the mechanism that senses volume changes is not known. Preincubation of Dunaliella salina with tridemorph, a specific inhibitor of sterol biosynthesis, inhibits glycerol synthesis and volume recovery. The inhibition is associated with suppression of [14C]bicarbonate incorporation into sterols and is correlated with pronounced depletion of plasma membrane sterols. Incubation of sterol-depleted cells with cholesterol hemisuccinate restores the capacity for volume regulation in response to hyperosmotic stress. Tridemorph as well as lovastatin also inhibit volume changes that are induced by high light in Dunaliella bardawil, a species that responds to high light intensity by synthesis of large amounts of [beta]-carotene. These volume changes result from accumulation of glycerol and are associated with de novo synthesis of sterols. The major plasma membrane sterol in D. salina and the high-light-induced sterol in D. bardawil co-migrate with ergosterol on thin-layer chromatography and on reversed-phase high-performance liquid chromatography. These results suggest that the osmosensory mechanism in Dunaliella resides in the plasma membrane, and that sterols have an important role in sensing osmotic changes.

Capillary and mitochondrial support of neural plasticity in adult rat visual cortex.

Young adult rats (60 days old) were placed in complex environments (EC) or kept in individual cages (IC) for 10, 30, or 60 days. Previously reported findings in these same animals of synaptogenesis, decreased neuronal density, and increased cortical thickness in the EC animals demonstrated that cortical volume substantially expanded after 30 days. Such expansion would have spread apart existing capillaries and mitochondria, thereby diluting metabolic support. However, capillary spacing and mitochondrial volume fraction were maintained in these EC animals after 30 days, suggesting that new capillaries and mitochondria had infiltrated the tissue. Furthermore, many small vessels appeared after 10 days of complex experience, followed by expansion in vessel size until vessels from rats in EC for 60 days were larger than those from rats in IC for 60 days. The findings of constant vessel spacing in the face of expanding tissue volume, along with a set of small vessels that subsequently increased in size, suggest that small-sized new vessels were introduced in EC cortex by 10 days but had not matured in size until after 30 days. The results indicate that young adult rats can generate new capillaries and mitochondria in response to increased metabolic demands, but in a less vigorous fashion than in previously described weanling animals.