Riding out the storm: depleted fat stores and elevated hematocrit in a small bodied endotherm exposed to severe weather.

In the mid-continental grasslands of North America, climate change is increasing the intensity and frequency of extreme weather events. Increasingly severe storms and prolonged periods of elevated temperatures can impose challenges that adversely affect an individual's condition and, ultimately, survival. However, despite mounting evidence that extreme weather events, such as heavy rain storms, can impose short-term physiological challenges, we know little regarding the putative costs of such weather events. To determine the consequences of extreme weather for small endotherms, we tested predictions of the relationships between both severe precipitation events and wet bulb temperatures (an index that combines temperature and humidity) prior to capture with body composition and hematocrit of grasshopper sparrows (Ammodramus savannarum) caught during the breeding season at the Konza Prairie Biological Station, Kansas, USA, between 2014 and 2016. We measured each individual's fat mass, lean mass and total body water using quantitative magnetic resonance in addition to their hematocrit. Individuals exposed to storms in the 24 hours prior to capture had less fat reserves, more lean mass, more water and higher hematocrit than those exposed to moderate weather conditions. Furthermore, individuals stored more fat if they experienced high wet bulb temperatures in the week prior to capture. Overall, the analysis of these data indicate that extreme weather events take a physiological toll on small endotherms, and individuals may be forced to deplete fat stores and increase erythropoiesis to meet the physiological demands associated with surviving a storm. Elucidating the potential strategies used to cope with severe weather may enable us to understand the energetic consequences of increasingly severe weather in a changing world.

Estimated Clinical Trial Capacity of Sites Participating in the COVID-19 Convalescent Plasma Expanded Access Program.

This cross-sectional study estimates the trial capacity of sites participating in the COVID-19 convalescent plasma expanded access program.

IL-10 induces the development of immunosuppressive CD14(+)HLA-DR(low/-) monocytes in B-cell non-Hodgkin lymphoma.

The biological role of monocytes and macrophages in B-cell non-Hodgkin lymphoma (NHL) is not fully understood. We have previously reported that monocytes from patients with B-cell NHL have an immunosuppressive CD14(+)HLA-DR(low/-) phenotype that correlates with a poor prognosis. However, the underlying mechanism by which CD14(+)HLA-DR(low/-) monocytes develop in lymphoma is unknown. In the present study, we found that interleukin (IL)-10, which is increased in the serum of patients with B-cell NHL, induced the development of the CD4(+)HLA-DR(low/-) population. Using peripheral blood samples from patients with B-cell NHL, we found that absolute numbers of CD14(+) monocytic cells with an HLA-DR(low/-) phenotype were higher than healthy controls and correlated with a higher International Prognostic Index score. IL-10 serum levels were elevated in lymphoma patients compared with controls and were associated with increased peripheral monocyte counts. Treatment of monocytes with IL-10 in vitro significantly decreased HLA-DR expression and resulted in the expansion of CD14(+)HLA-DR(low/-) population. We found that lymphoma B cells produce IL-10 and supernatants from cultured lymphoma cells increased the CD14(+)HLA-DR(low/-) population. Furthermore, we found that IL-10-induced CD14(+)HLA-DR(low/-) monocytes inhibited the activation and proliferation of T cells. Taken together, these results suggest that elevated IL-10 serum levels contribute to increased numbers of immunosuppressive CD14(+)HLA-DR(low/-) monocytes in B-cell NHL.

Deficiencia adquirida del factor VIII. Un ejemplo cuando la cirugía puede ser perjudicial y no para salvar vidas / Deficiência adquirida do fator VIII. Um exemplo de quando a cirurgia pode ser prejudicial e nâo vinculada a salvar vidas / Acquired factor VIII deficiency. One instance when surgery may be harmful and not life-saving

La hemofilia adquirida A es una condición extremadamente rara que ocurre en una persona en un millón por año. Puede causar riesgo para la vida por causar episodios de sangrado durante la edad adulta, debido a la producción de auto-anticuerpos que inactivan el factor VIII. Su tratamiento suele incluir la inmunosupresión y la cirugía se debe evitar en lo posible. Presentamos dos casos que nos tocó tratar, y realizamos una recopilación somera de la bibliografia, a fin de enfatizar la necesidad de no realizar tratamiento quirúrgico en estos casos.

A hemofilia adquirida A é uma condição extremamente rara que pode ocorrer com a probabilidade de um caso em um milhão de pessoas por ano. Pode causar risco para a vida por causar episódios de sangramento durante a idade adulta, devido à produção de autoanticorpos que inativam o fator VIII. Seu tratamento geralmente inclui a imunosupressão, e a cirurgia deve, dentro do possível, ser evitada. Apresentamos dois casos por nós tratados, e realizamos um breve resumo da bibliografia, com a finalidade de enfatizar o propósito de não realizar tratamento cirúrgico nestes casos.

Acquired hemophilia A is an extremely rare disease with an incidence of 1 in 1,000,000 per year. It may be life threatening as it produces bleeding episodes in adult life, due to the production of antibodies which inactivate factor VIII. Treatment may include immunosuppression and surgery must be avoided as much as possible. We shall present two of our cases and then make a brief review of the literature, in order to underscore the need of not operating these cases.

Abdominal wall reconstruction in patients with enterocutaneous fistulas.

Enterocutaneous fistulas (ECFs) remain a feared complication of surgery, particularly in acute care and trauma patients. Despite advances in medical and surgical therapies, ECFs are associated with significant morbidity and mortality; in addition, significant health care resources are consumed in their treatment. Because of the frequency nowadays of open-abdomen and damage-control surgery, of aggressive treatment for abdominal compartment syndrome, and of necrotizing soft tissue infections of the abdominal wall, ECFs are becoming common; so are enteroatmospheric fistulas (EAFs), which represent a new entity where the lumen of the intestine is directly exposed to the outside environment and has no track through subcutaneous or cutaneous tissue. The surgical management of abdominal wall defects, including ECFs and/or EAFs, is often associated with major hernias and other complexities. Careful planning and advanced surgical techniques are required, often involving the use, alone or in combination, of biologic mesh and composite tissue transfer. The treatment of ECFs in patients with large abdominal wall defects is challenging, but with proper techniques, the results can be excellent. Biologic mesh is the mesh of choice in such patients.

Differential regulation of growth and checkpoint control mediated by a Cdc25 mitotic phosphatase from Pneumocystis carinii.

Pneumocystis carinii is an opportunistic fungal pathogen phylogenetically related to the fission yeast Schizosaccharomyces pombe. P. carinii causes severe pneumonia in immunocompromised patients with AIDS and malignancies. Although the life cycle of P. carinii remains poorly characterized, morphologic studies of infected lung tissue indicate that P. carinii alternates between numerous small trophic forms and fewer large cystic forms. To understand further the molecular mechanisms that regulate progression of the cell cycle of P. carinii, we have sought to identify and characterize genes in P. carinii that are important regulators of eukaryotic cell cycle progression. In this study, we have isolated a cDNA from P. carinii that exhibits significant homology, but unique functional characteristics, to the mitotic phosphatase Cdc25 found in S. pombe. P. carinii Cdc25 was shown to rescue growth of the temperature-sensitive S. pombe cdc25-22 strain and thus provides an additional tool to investigate the unique P. carinii life cycle. Although P. carinii Cdc25 could also restore the DNA damage checkpoint in cdc25-22 cells, it was unable to restore fully the DNA replication checkpoint. The dissociation of checkpoint control at the level of Cdc25 indicates that Cdc25 may be under distinct regulatory control in mediating checkpoint signaling.

The effects of readers' goals on inference generation and memory for texts.

We investigated the effects of readers' goals on inference generation and memory for expository text. College students (N = 82) read texts for the purpose of either study or entertainment. On-line inference generation was recorded via think-aloud procedures, and off-line memory was assessed via free recall. Reading goal strongly influenced inferential activity: Readers with a study goal produced more coherence-building (i.e., backward/explanatory and forward/predictive) inferences, whereas readers with an entertainment goal produced more associations and evaluations. These differences were associated with superior memory for the texts in the study condition. The results indicate that inference generation during reading is partly strategic and is influenced systematically by reading purpose. We propose that reading goals influence readers' standards of coherence, which in turn influence the types of inferences that they draw and the final memory representations that they construct.

Induction of calcitonin and calcitonin receptor expression in rat mammary tissue during pregnancy.

Human breast milk samples at early time points after parturition contain high levels of calcitonin (CT) in both normal and thyroidectomized mothers, suggesting that mammary tissue produces CT. Using blot hybridization and reverse-transcriptase polymerase chain (RT-PCR) analysis of rat mammary RNA we found that CT messenger RNA is induced at midpregnancy (day 12), remains elevated through late pregnancy (day 19) but then decreases before the day of birth. RIA of mammary CT revealed that levels increase from 0.3 ng/g tissue in nonpregnant animals to peak at 1.6 ng/g on day 19 and then decline after that, paralleling messenger RNA expression. Dilution profiles for extracted mammary CT showed close parallelism with monomeric rat CT. Plasma samples from thyroparathyroidectomized rats contained 10-20 pg/ml CT that did not increase during pregnancy, suggesting that mammary CT is not released into plasma but functions locally. Consistent with this, RT-PCR detected that the CT receptor C1a isoform is expressed in rat mammary tissues during both pregnancy and lactation. This is the first report that mammary tissue expresses both CT and the CT receptor during pregnancy, suggesting that CT may have a paracrine regulatory role in the mammary gland.

Survivors of catastrophic illness: outcome after direct transfer from intensive care to extended care facilities.

OBJECTIVE: To describe outcomes of adult survivors of prolonged critical illness after direct transfer to extended care facilities. DESIGN: A retrospective cohort study. SETTING: All adult intensive care units (ICUs) in a tertiary care university hospital. PATIENTS: A consecutive series of 97 adult survivors with an ICU stay of > or =7 days transferred directly from intensive care to extended care facilities between 1990 and 1996. INTERVENTIONS: None. METHODS AND MAIN RESULTS: Hospital and extended care facility charts were reviewed for patient characteristics, resource utilization, and survival. Survivors were for a minimum of 1 yr and a maximum of 6 yrs, and were interviewed to assess quality of life and functionality. The mean age of the patients was 66+/-16 (range, 19-93) yrs. The median length of ICU stay for these patients was 39 (range, 7-276) days. Only 18 of the 71 ventilator-assisted patients were weaned from mechanical ventilation after transfer to the extended care facility. Survival for the study period, at 1 yr after discharge from the ICU, was 49.5%. One year after discharge from the ICU, 11.5% of all patients had returned home, were breathing spontaneously, had a fair or better quality of life, and had good physical functionality. Each successive year, an increasing proportion of patients underwent direct transfer to an extended care facility. This strategy decreased the patients' length of stay (p<.002) in the ICU from year to year, but was significantly associated with an increase in readmissions to acute care hospitals (p<.002). CONCLUSIONS: Survivors of catastrophic illness who are so debilitated that they require transfer to an extended care facility have a low likelihood of achieving both survival and functional independence 1 yr after discharge from the ICU. Aggressive cost-conscious strategies to accelerate the transfer of these patients successfully reduced the length of ICU stay and hospital costs, but were associated with a high rate of readmission to tertiary care facilities.

Tracheal reconstruction using alcohol-stored homologous cartilage and autologous cartilage in the rabbit model.

OBJECTIVE: Reconstruction of laryngotracheal stenosis continues to pose a significant challenge. Cartilage grafts have been in use for almost a century, but despite good clinical results, many questions concerning the survival and growth of implanted cartilage persist. To reduce donor site morbidity, the use of homologous cartilage has been investigated. This study compared alcohol-stored homologous auricular cartilage with autologous auricular cartilage for anterior graft laryngotracheal reconstruction in a rabbit model. METHODS: Autologous and alcohol preserved homologous auricular cartilage was transplanted to the resected anterior tracheal wall of the twenty New Zealand rabbits. Rabbits were sacrificed 6 weeks after surgery and histologic analysis was performed on the implanted cartilage grafts. RESULTS: The autografts were significantly more likely than the homografts to demonstrate viable cells (95% vs. 30%, P<0.05) and less likely to exhibit significant resorption, fibrosis or necrosis (P<0.05). Resorption and necrosis were most common in areas of trauma to the graft. Complete epithelialization occurred in all of the autografts but in only 65% of the homografts (P<0.05). New cartilage formation and integration of the implanted grafts was poor with both types of grafts. CONCLUSION: Autologous cartilage appears to have better survival than alcohol preserved homologous cartilage when used for anterior graft laryngotracheal reconstruction in a rabbit model.

Blood safety. The Food and Drug Administration's role.

The federal government has a role in protecting consumers from threats to the blood supply. These threats range from the residual risks of known infection, to emerging infections that may contaminate the blood supply, to complacency in the area of adherence to product standards and Current Good Manufacturing Practices. The Food and Drug Administration is tasked with oversight of the safety of the nation's blood supply. The Food and Drug Administration's regulation of blood and blood components includes preapproval for products entering interstate commerce and adherence to Current Good Manufacturing Practices for all blood components. Oversight for Current Good Manufacturing Practices compliance includes inspection and reporting requirements. These regulatory programs are coupled with the Public Health Service's ongoing research and epidemiological surveillance. The goals of these programs are to prevent another infectious disease epidemic from infecting the blood supply as did the acquired immunodeficiency syndrome in the early 1980s and to further improve blood safety.

Pneumocystis carinii contains a functional cell-division-cycle Cdc2 homologue.

Pneumocystis carinii causes life-threatening pneumonia in immunocompromised patients. The inability to culture P. carinii has hampered basic investigations of the organism's life cycle, limiting the development of new therapies directed against it. Recent investigations indicate that P. carinii is a fungus phylogenetically related to other ascomycetes such as Schizosaccharomyces pombe. The cell cycles of S. pombe and homologous fungi are carefully regulated by cell-division-cycle molecules (cdc), particularly cell-division-cycle 2 (Cdc2), a serine-threonine kinase with essential activity at the G1 restriction point and for entry into mitosis. Antibodies to the proline-serine-threonine-alanine-isoleucine-arginine (PSTAIR) amino-acid sequence conserved in Cdc2 proteins specifically precipitated, from P. carinii extracts, a molecule with kinase activity consistent with a Cdc2-like protein. Cdc2 molecules exhibit differential activity throughout the life cycle of the organisms in which they occur. In accord with this, the P. carinii Cdc2 showed greater specific activity in P. carinii trophic forms (trophozoites) than in spore-case forms (cysts). In addition, complete genomic and complementary DNA (cDNA) sequences of P. carinii Cdc2 were cloned and found to be most closely homologus to the corresponding sequences of other pathogenic fungi. The function of P. carinii cdc2 cDNA was further documented through its ability to complement the DNA of mutant strains of S. pombe with temperature-sensitive deficiencies in Cdc2 activity. The P. carinii cdc2 cDNA restored normal Cdc2 function in these mutant strains of S. pombe, and promoted fungal proliferation. These studies represent the first molecular analysis of the cell-cycle-regulatory machinery in P. carinii. Further understanding of P. carinii's life cycle promises novel insights for preventing and treating the intractable infection it causes in immunocompromised patients.

Measurements of serum müllerian inhibiting substance in the evaluation of children with nonpalpable gonads.

BACKGROUND: Müllerian inhibiting substance, produced constitutively by the prepubertal testes, promotes involution of the müllerian ducts during normal male sexual differentiation. In children with virilization and nonpalpable gonads, only those with testicular tissue should have detectable serum concentrations of müllerian inhibiting substance. METHODS: We measured serum mullerian inhibiting substance in 65 children with virilization at birth and nonpalpable gonads (age at diagnosis, 2 days to 11 years) and serum testosterone in 54 of them either after the administration of human chorionic gonadotropin or during the physiologic rise in testosterone that occurs in normal infants. RESULTS: The mean (+/-SD) serum mullerian inhibiting substance concentration in the 17 children with no testicular tissue was 0.7+/-0.5 ng per milliliter, as compared with 37.5+/-39.6 ng per milliliter in the 48 children with testes (P<0.001). In the latter group, the mean values in the 14 children with abnormal testes and the 34 with normal testes were 11.5+/-11.8 and 48.2+/-42.1 ng per milliliter, respectively (P< 0.001). The sensitivity and specificity of the serum müllerian inhibiting substance assay for detecting the absence of testicular tissue were 92 percent and 98 percent, respectively, as compared with 69 percent and 83 percent for the measurement of serum testosterone. Furthermore, measurement of serum mullerian inhibiting substance was more sensitive than serum testosterone measurement for the identification of children with abnormal testes (67 percent vs. 25 percent), whereas the specificity of the two tests was similar. CONCLUSIONS: Measurements of serum mullerian inhibiting substance can be used to determine testicular status in prepubertal children with nonpalpable gonads, thus differentiating anorchia from undescended testes in boys with bilateral cryptorchidism and serving as a measure of testicular integrity in children with intersexual anomalies.

Toxicity of white phosphorus to waterfowl: acute exposure in mallards.

As part of an effort to understand extensive, white phosphorus (P4)-induced waterfowl mortality at Eagle River Flats, Fort Richardson, Alaska (USA), we conducted a number of acute toxicity tests using penned mallards (Anas platyrhynchos) in 1993 and 1994. The 24-hr median lethal dose (LD50) for P4 dissolved in oil was 6.46 mg/kg in adult males and 6.96 mg/kg in adult females. Although the median lethal doses were not statistically different, the female dose-response curve had a statistically shallower slope than that of males. The LD50 for the ecologically more relevant pelletized form of P4 in adult males was 4.05 mg/kg. In mallards, one mechanism of P4 toxicity caused rapid (3 to 10 hr) mortality and had signs consistent with anoxia. A second, slower acting mechanism resulted in hepatic and renal pathology including extensive fat deposition in the liver and cellular necrosis. White phosphorus accumulated in adipose tissues, but only for a few days.