Loss of function of male-specific lethal 3 (Msl3) does not affect spermatogenesis in rodents.

BACKGROUND: Male-specific lethal 3 (Msl3) is a member of the chromatin-associated male-specific lethal MSL complex, which is responsible for the transcriptional upregulation of genes on the X chromosome in males of Drosophila. Although the dosage complex operates differently in mammals, the Msl3 gene is conserved from flies to humans. Msl3 is required for meiotic entry during Drosophila oogenesis. Recent reports indicate that also in primates, Msl3 is expressed in undifferentiated germline cells before meiotic entry. However, if Msl3 plays a role in the meiotic entry of mammals has yet to be explored. RESULTS: To understand, if Msl3a plays a role in the meiotic entry of mammals, we used mouse spermatogenesis as a study model. Analyses of single-cell RNA-seq data revealed that, in mice, Msl3 is mostly expressed in meiotic cells. To test the role of Msl3 in meiosis, we used a male germline-specific Stra8-iCre driver and a newly generated Msl3flox conditional knock-out mouse line. Msl3 conditional loss-of-function in spermatogonia did not cause spermatogenesis defects or changes in the expression of genes related to meiosis. CONCLUSIONS: Our data suggest that, in mice, Msl3 exhibits delayed expression compared to Drosophila and primates, and loss-of-function mutations disrupting the chromodomain of Msl3 alone do not impede meiotic entry in rodents.

Dyspnea, anxiety, body consciousness, and quality of life in patients with lung cancer.

Dyspnea is a common symptom of lung cancer that can impact patient physical, social, and psychological well-being. Study goals were to evaluate quality of life (QOL) and dyspnea in patients with lung cancer and the relationships between QOL, dyspnea, trait anxiety, and body consciousness. Sociodemographic and cancer-related variables (stage, cell type, performance status) were evaluated. One hundred twenty outpatients with stage I-IV lung cancer participated in the study. Patients completed 5 questionnaires assessing QOL, dyspnea, trait anxiety, body consciousness, and pain. Eighty-seven percent of study participants experienced dyspnea. Patients with high dyspnea scores had lower QOL (P = 0.04). Dyspnea was worse in men than in women (P = 0.02), and there was a trend towards older patients reporting more severe dyspnea than younger patients (P = 0.06). There was no difference in dyspnea based on cancer stage, cell type, or performance status. Pain and anxiety scores were higher in patients with high dyspnea (P = 0.02, P = 0.03). Dyspnea was more severe in patients taking opioid analgesics when compared to non-opioids or no pain medications (P = 0.03). No significant association was found between dyspnea, anxiety, and private body consciousness.

Distribution and severity of bronchiectasis in allergic bronchopulmonary aspergillosis (ABPA).

The purpose of this paper was to quantitate the distribution and severity of computed tomography (CT) and radiographic findings in patients with allergic bronchopulmonary aspergillosis (ABPA), probable ABPA, and asthmatic controls. Chest radiographs and high-resolution CT images were evaluated in 19 patients with documented ABPA and 18 asthmatic controls. Ten patients with probable ABPA were also evaluated. On CT examination 17 patients (89%) with ABPA had central cystic or varicoid bronchiectasis in at least one lobe. One patient had no evidence for bronchiectasis. Three asthmatic patients (17%) had findings of cylindrical bronchiectasis. All 10 patients with probable ABPA had evidence of bronchiectasis on high-resolution CT (HRCT). The majority of patients with ABPA have diffuse disease at the time of diagnosis, manifested by central cystic and/or varicoid bronchiectasis in four or five lobes. Evaluation with HRCT can facilitate a diagnosis of ABPA and probable ABPA, allowing for earlier treatment which may prevent progression to fibrosis.

Increased formation of thromboxane in vivo in humans with mastocytosis.

Clinical manifestations of mastocytosis are mediated, at least in part, by release of the mast cell mediators histamine and prostaglandin D2. It has been previously reported that in addition to prostaglandin D2, mast cells produce other eicosanoids, including thromboxane. Nonetheless, little information exists regarding the formation of other prostanoids in vivo. The most accurate method to examine the systemic production of eicosanoids in vivo is the quantitation of urinary metabolites. We previously developed a highly accurate assay employing mass spectrometry to measure a major urinary metabolite of thromboxane, 11-dehydro-thromboxane B2, in humans. We utilized this assay to quantitate thromboxane production in 17 patients with histologically proven mastocytosis. We report that thromboxane formation was significantly increased (>2 SD above the mean) in at least one urine sample from 65% of patients studied. Of these, 91% of patients with documented systemic involvement had elevated thromboxane generation. In addition, endogenous formation of thromboxane was highly correlated with the urinary excretion of the major urinary metabolite of prostaglandin D2 (r = 0.98) and Ntau-methylhistamine (r = 0.91), suggesting that the cellular source of increased thromboxane in vivo could be the mastocyte. Enhanced thromboxane formation in patients with this disorder is unlikely to be of platelet origin as other markers of platelet activation, platelet factor 4 and beta-thromboglobulin, were not increased in three patients with marked overproduction of thromboxane. Furthermore, the recovery of 11-dehydro-thromboxane B2 excretion in two patients after the administration of aspirin occurred significantly more rapidly than the recovery of platelet thromboxane generation. These studies, therefore, report that thromboxane production is significantly increased in the majority of patients with mastocytosis that we examined and provide the basis to elucidate the role of this eicosanoid in disorders of mast cell activation.

Arthritis health service utilization among the elderly: the role of urban-rural residence and other utilization factors.

OBJECTIVE: To compare the impact of urban-rural residence and other factors on the utilization of any type of arthritis-related physician care and on rheumatologist utilization. METHODS: A population-based random sample of adults 65 years of age or older with self-reported arthritis from 10 urban and 12 rural Iowa counties were surveyed by telephone interview. We estimated the arthritis prevalence and health service utilization in this sample and evaluated the effects of predisposing, enabling, and need factors on utilization and satisfaction. Health care utilization was defined as ever having visited specific types of providers for arthritis-related care. RESULTS: A total of 488 individuals participated: 227 from urban counties and 261 rural respondents. Urban respondents more commonly reported having received a diagnosis of osteoarthritis from their physicians but were less likely to report rheumatoid arthritis. A greater proportion of urban versus rural respondents had utilized any physician for arthritis care (50.7% versus 41.0%, P = 0.032) and had more often seen an orthopedist (18.1% versus 9.6%, P = 0.006) or general internist (18.5% versus 8.8%, P = 0.002). A diagnosis of rheumatoid arthritis, younger age, living with another person, higher income, and further distance from an arthritis provider were significantly associated with prior rheumatologist utilization. The strongest adjusted predictor of any physician visit for arthritis care was whether older adults drove themselves to their provider. For rheumatologist utilization, a diagnosis of rheumatoid arthritis and age were independently associated. CONCLUSIONS: The most striking finding was the consistent association of need factors (such as the desire for medical advice), joint swelling, and the presence of a diagnosis of rheumatoid arthritis with physician utilization. We identified significant urban-rural variations in factors both enabling and predisposing to arthritis care, although urban-rural status did not appear to independently influence arthritis physician utilization. In a rural state with a relatively small number of rheumatologists, deleterious enabling factors such as greater distance from the doctor and lack of supplemental insurance did not provide significant obstacles to either rheumatologist or generalist utilization.

Level of uncompensated care delivered by emergency physicians in Florida.

STUDY OBJECTIVES: To determine selected characteristics of patients who present for care in emergency departments in Florida, the proportion who appear to be uninsured or underinsured, and the magnitude of uncompensated care provided by the emergency physicians in selected EDs in Florida. DESIGN: Retrospective analysis of billing data. SETTING: Twenty-five EDs in Florida. MAIN RESULTS: Uninsured patients comprised 20.6% of the sample. Emergency and urgent patients were 39.9% of the sample. The overall collection ratio was 59.2%. CONCLUSION: Emergency physicians provide substantial amounts of uncompensated care.

Induction of estrogen receptor and reversal of the nuclear/cytoplasmic receptor ratio during vitellogenin synthesis and withdrawal in Xenopus laevis.

The levels of cytoplasmic and nuclear estrogen receptor have been determined in livers of male Xenopus laevis stimulated by estradiol-17 beta to synthesize vitellogenin mRNA. Estrogen receptor levels were also determined in unstimulated liver and following long term withdrawal of estrogen. In unstimulated liver cells, which do not contain detectable vitellogenin mRNA, more than 80% of the estrogen receptor is located in the nucleus (550 high affinity estrogen binding sites/nucleus), while the cytoplasm contains only 100 high affinity estrogen binding sites/cell. Administration of estradiol-17 beta, which induces massive synthesis and accumulation of vitellogenin mRNA, induces the estrogen receptor as well. The nuclear receptor level rises to approximately 2,000 estrogen binding sites/cell, while the cytosol receptor increases to only 150 sites/cel. Liver cells of male X. laevis which have been withdrawn from estrogen for 70 days exhibit a striking change in receptor levels. The nuclear receptor returns to the level prevailing in unstimulated cells (approximately 500 sites/cell) while the cytosol receptor level rises to more than 1,200 sites/cell (equivalent to 260 fmol/g of tissue). The existence of a pool of cytosol receptor, which is rapidly available for induction of vitellogenin mRNA, may in part explain the shorter lag period and more rapid induction of vitellogenin mRNA observed during secondary estrogen stimulation of withdrawn Xenopus liver cells.