Author Correction: Proteomic and Transcriptomic Changes in Hibernating Grizzly Bears Reveal Metabolic and Signaling Pathways that Protect against Muscle Atrophy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Proteomic and Transcriptomic Changes in Hibernating Grizzly Bears Reveal Metabolic and Signaling Pathways that Protect against Muscle Atrophy.

Muscle atrophy is a physiological response to disuse and malnutrition, but hibernating bears are largely resistant to this phenomenon. Unlike other mammals, they efficiently reabsorb amino acids from urine, periodically activate muscle contraction, and their adipocytes differentially responds to insulin. The contribution of myocytes to the reduced atrophy remains largely unknown. Here we show how metabolism and atrophy signaling are regulated in skeletal muscle of hibernating grizzly bear. Metabolic modeling of proteomic changes suggests an autonomous increase of non-essential amino acids (NEAA) in muscle and treatment of differentiated myoblasts with NEAA is sufficient to induce hypertrophy. Our comparison of gene expression in hibernation versus muscle atrophy identified several genes differentially regulated during hibernation, including Pdk4 and Serpinf1. Their trophic effects extend to myoblasts from non-hibernating species (including C. elegans), as documented by a knockdown approach. Together, these changes reflect evolutionary favored adaptations that, once translated to the clinics, could help improve atrophy treatment.

No additive effects of inhaled iloprost and prone positioning on pulmonary hypertension and oxygenation in acute respiratory distress syndrome.

BACKGROUND: In acute respiratory distress syndrome (ARDS), pulmonary hypertension is associated with a poor prognosis. Prone position is effective to improve oxygenation whereas inhaled iloprost can treat pulmonary hypertension. However, combination of these interventions has not been examined before. The hypothesis was that this combination had additive effects on oxygenation and pulmonary hemodynamics as compared with each intervention alone. METHODS: In a prospective, randomized cross-over study, ten pigs were anesthetized, intubated and ventilated with volume controlled ventilation. Carotid, jugular venous and pulmonary artery catheters were inserted. ARDS was induced with oleic acid (0.20 mL/kg). Measurements were repeated in randomized different sequences of prone or supine positions with or without iloprost inhalation (220 ng/kg/min) (four combinations). Systemic and pulmonary arterial pressures; arterial and mixed venous blood gases; and Qs/Qt and the resistances were recorded. RESULTS: Iloprost decreased pulmonary artery pressures (for MPAP: P=0.034) in both supine (37±10 vs. 31±8 mmHg; P<0.05) and prone positions (38±9 vs. 29±8 mmHg; P<0.05); but did not obtain a significant improvement in oxygenation in both positions. Prone position improved the oxygenation (p<0.0001) compared to supine position in both with (361±140 vs. 183±158 mmHg, P<0.05) or without iloprost application (331±112 vs. 167±117 mmHg, P<0.05); but did not achieve a significant decrease in MPAP. CONCLUSION: Although iloprost reduced pulmonary arterial pressures, and prone positioning improved oxygenation; there are no additive effects of the combination of both interventions on both parameters. To treat both pulmonary hypertension and hypoxemia, application of iloprost in prone position is suggested.

Perceptions of HPV and cervical cancer among Haitian immigrant women: implications for vaccine acceptability.

INTRODUCTION: Women in Haiti and throughout the Haitian Diaspora shoulder a disproportionate burden of cervical cancer morbidity and mortality. The widespread Human Papillomavirus (HPV) vaccination holds promise for helping to attenuate this disparity. However, previous research has not fully examined Haitian women's perceptions of, and barriers to, HPV vaccination, which is essential for informing future intervention. The current paper aims to fill this gap. METHODS: As part of ongoing Community-Based Participatory Research (CBPR) efforts, we conducted a series of focus groups with Haitian immigrant women in Little Haiti, the predominantly Haitian neighborhood in Miami, Florida, U.S. Focus group questions assessed women's knowledge and beliefs about cervical cancer and HPV, their opinions of vaccines in general, their knowledge and perceptions of the HPV vaccine specifically and health communications preferences for cervical cancer prevention. RESULTS: Among the participants who had heard of HPV, many held misconceptions about virus transmission and did not understand the role of HPV in the development of cervical cancer. Virtually all participants expressed support for vaccines in general as beneficial for health. Some women had heard of the HPV vaccine, primarily as the result of a contemporary popular media campaign promoting the Gardasil® vaccine. Physician recommendation was commonly mentioned as a reason for vaccination, in addition to having more than one sex partner. Women felt the HPV vaccine was less appropriate for adolescent girls who are presumed as not sexually active. Women indicated a strong preference to obtain health information through trusted sources, such as Haitian physicians, Haitian Community Health Workers, and especially Kreyol-language audiovisual media. DISCUSSION: Study findings indicate a need for culturally and linguistically appropriate educational initiatives to promote awareness of HPV and its role in cervical cancer, the importance of vaccination against the virus, explicitly differentiating HPV from HIV and providing specific information about vaccine safety. CONCLUSION: In the U.S., there is a substantial lack of educational information available in Haitian about HPV and cervical cancer. This gap results in missed opportunities to promote disease prevention through vaccination and regular screening. Addressing such gaps is essential for achieving health equity among Haitian immigrant women and other, similarly underserved women, who are disproportionately burdened by cervical cancer.

Comparison of equipotent doses of ropivacaine-fentanyl and bupivacaine-fentanyl in spinal anaesthesia for lower abdominal surgery.

The aim of this randomised, double-blind study was to compare equipotent doses of plain ropivacaine and bupivacaine (19.5 mg and 13 mg respectively), both with fentanyl 20 microg, for spinal anaesthesia in lower abdominal surgery. After written informed consent had been obtained, 52 ASA I to II male patients scheduled for lower abdominal surgery were randomly assigned to receive intrathecal plain ropivacaine 19.5 mg with fentanyl 20 microg (group R, n =26) or plain bupivacaine 13 mg with fentanyl 20 microg (group B, n =26) in 3 ml. The level and duration of sensory block, intensity and duration of motor block, time to mobilise and patient satisfaction were recorded. All patients achieved sensory block to T10 or higher The level of sensory block was significantly higher in group B (T4 [T3 to T7] vs T7 [T4 to T9], P <0.05). There was no difference in the onset time of motor block. The duration of motor block (Bromage score >0) was shorter in group R (139+/-39 minutes vs group B 182+/-46 minutes, P <0.05). The duration and intensity of complete motor block (Bromage score=3) were also shorter in group R (90+/-25 minutes vs 130+/-40 minutes, P <0.05). We conclude that plain ropivacaine 19.5 mg plus fentanyl 20 microg is associated with a lower level of sensory block and a shorter duration of motor block when compared to bupivacaine 13 mg plus fentanyl 20 microg for spinal anaesthesia in lower abdominal surgery.

Generalizability of toxicity data from oncology clinical trials to clinical practice: toxicity of irinotecan-based regimens in patients with metastatic colorectal cancer.

BACKGROUND: The relevance of oncology trial results to clinical practice depends on whether the trial participants are similar to the actual population of patients receiving treatment for the malignancy and whether the patients are treated similarly in both circumstances. Chemotherapy treatments may be more toxic in patients of advanced age and poor performance status-patients typically excluded from clinical trials. METHODS: In a retrospective chart review that included all non-trial patients with metastatic colorectal cancer treated with irinotecan-based chemotherapy from January 2004 to September 2006 at our institution, we quantified and subsequently compared the toxicity rates of the irinotecan regimens in clinical practice with published toxicity rates from corresponding phase iii clinical trials. The primary endpoint was the incidence of grades 3 and 4 diarrhea. RESULTS: The study included 203 patients, and the irinotecan regimens considered included FOLFIRI [irinotecan, leucovorin, 5-fluorouracil (5fu)],IFL (bevacizumab, irinotecan, 5FU, leucovorin),XELIRI (capecitabine, 3-weekly irinotecan), andirinotecan monotherapy. The rates of grades 3 and 4 diarrhea for FOLFIRI, IFL, XELIRI, and irinotecan monotherapy in clinical practice were 10%, 15%, 17%, and 21% as compared with 10%, 23%, 20%, and 31% respectively in clinical trials. When only patients meeting trial performance status and age criteria were analyzed, the rates of grades 3 and 4 diarrhea by regimen were 11%, 20%, 19%, and 26% respectively. CONCLUSIONS: Overall, the toxicity rates for FOLFIRI and irinotecan monotherapy in non-trial patients were not statistically different from the rates quoted in published clinical trials.

Differences in clinical presentation of deep vein thrombosis in men and women.

BACKGROUND: As assessment of clinical pretest probability is the first step in the diagnostic evaluation of deep vein thrombosis (DVT), it is important to know if the clinical features of DVT are the same in men and women. OBJECTIVES: To compare the prevalence and clinical characteristics of DVT, and the accuracy of clinical pretest probability assessment, between men and women with suspected DVT. METHODS: A retrospective analysis of individual patient data from three prospective studies by our group that evaluated diagnostic tests for a suspected first episode of DVT. Clinical characteristics, clinical pretest probability for DVT, and prevalence and extent of DVT was assessed in a total of 1838 outpatients. RESULTS: The overall prevalence of DVT was higher in men than in women (14.4% vs. 9.4%) (P = 0.001). The prevalence of DVT was higher in men than in women who were categorized as having a clinical pretest probability that was low (6.9% vs. 3.5%; P = 0.025) or moderate (16.9% vs. 8.7%; P = 0.04), but similar in patients in the high category (40.2% vs. 44.0%; P = 0.6). In patients diagnosed with DVT, swelling of the entire leg occurred more often (41.5% vs. 15.7%; P < 0.001), and thrombosis was more extensive (involvement of both popliteal and common femoral veins in 47.9% vs. 21.6%), in women than in men. CONCLUSIONS: In outpatients with suspected DVT, the overall prevalence of thrombosis and the prevalence of thrombosis in those with a low or a moderate clinical pretest probability were higher in men than in women.

Comparison of the effects of thoracic and lumbar epidural anaesthesia on induction and maintenance doses of propofol during total i.v. anaesthesia.

BACKGROUND: In this randomized, double-blind study, the effects of thoracic and lumbar epidural anaesthesia on the induction doses (IDs) and maintenance doses (MDs) of propofol during bispectral index (BIS) guided total i.v. anaesthesia were compared. METHODS: Fifty-four patients (three groups, n=18 each) undergoing urological surgery in lumbotomy position were studied in Groups T (Th7-8) and L (L3-4), epidural anaesthesia was performed with initial doses obtaining sensorial block at Th4 (sd 1) followed by 7 ml h(-1) infusion; Group C received no epidural anaesthesia intraoperatively. The ID (BIS <45) and MD (BIS: 40-50) of propofol and recovery (BIS >80) and extubation times were recorded. RESULTS: The volume to obtain a block was significantly lower in Group T than in Group L [10.7 (1.5) vs 14.7 (1.0) ml; P<0.001]. ID was significantly higher in Group C compared with that in Groups T and L [2.16 (0.15) vs 1.33 (0.19) vs 1.46 (0.14) mg kg(-1), respectively; P<0.001] with no significant difference between Groups T and L. For MD, there were significant differences between all groups [3.82 (0.9) vs 5.8 (1.32) vs 9.21 (0.55) mg kg(-1) h(-1) in Groups T, L, and C, respectively; P<0.001]. For recovery and extubation times, Group T

Performance of creatinine clearance equations on the original Cockcroft-Gault population.

BACKGROUND: Prediction of endogenous creatinine clearance by mathematical equations such as the Cockcroft-Gault formula is used in clinical practice in spite of the reported concern for their limited predictability. The aim of this study is to determine whether the measured creatinine clearance can be predicted accurately by a number of published equations including the recently modified Cockcroft-Gault formula = Cockcroft-Gault formula x 1.73 m2/body surface area from the original Cockcroft-Gault population. METHODS: The performance of the mathematical equations in patients with different creatinine clearance and body mass indices was assessed by computing accuracy at different percentiles, bias and precision from the original Cockcroft-Gault data. RESULTS: Refitting the modified formula to the Cockcroft-Gault data gave superior results compared to the original Cockcroft-Gault formula with an overall accuracy in the general and subgroup analysis above 70% agreement within 30% estimate of the measured creatinine clearance. On the other hand, analysis of the other equations, including the original Cockcroft-Gault, demonstrated a limited accuracy to predict creatinine clearance particularly in patients with creatinine clearance below 50 ml/min with an overall accuracy in less than 1/3 of the calculated creatinine clearance within 30% range from the measured creatinine clearance. CONCLUSION: The current creatinine clearance equations and even the original Cockcroft-Gault formula did not accurately predict the measured creatinine clearance. Normalization for body surface area in the original Cockcroft-Gault formula demonstrated more accuracy to estimate creatinine clearance, particularly in patients with diminished renal function and is recommended to physicians who wish to use the Cockcroft-Gault formula in their practice until more credible formulas are developed.

Pulmonary bovine-type tuberculosis in rabbits: bacillary virulence, inhaled dose effects, tuberculin sensitivity, and Mycobacterium vaccae immunotherapy.

This report elucidates four aspects of the immunology of pulmonary tuberculosis produced in rabbits: (i) the virulence of bovine-type tubercle bacilli, strain Ravenel S, (ii) systemic factors influencing the generation of visible primary pulmonary tubercles, (iii) differences in tuberculin sensitivity of rabbits and humans, and (iv) the effect of Mycobacterium vaccae immunotherapy on cavitary tuberculosis. Laboratory strain Ravenel S (ATCC 35720) was not fully virulent. Fully virulent strains produce one visible primary pulmonary tubercle for each three bacillary units inhaled. Strain ATCC 35720 produced one such tubercle for each 18 to 107 bacillary units inhaled, indicating that its virulence was reduced by 6- to 36-fold. When a low dose of this Ravenel S strain was inhaled, the host resistance (measured by the number of inhaled bacilli needed to generate one visible primary pulmonary tubercle) was increased at least 3.5-fold compared to the host resistance when a high dose was inhaled. Rabbits and humans differ in the degree and in the maintenance of their dermal sensitivities to tuberculin. Compared to rabbits, humans are 100 times more sensitive to tuberculin. Also, at 33 weeks rabbits with well-controlled cavitary tuberculosis usually showed a decrease in their tuberculin reactions of about 50% from peak values, whereas humans with such well-controlled tuberculosis are thought to maintain strong reactions for many years. These species differences may be due to desensitization to group II mycobacterial antigens in the rabbits because they have a different diet and a different type of digestive tract. M. vaccae immunotherapy of rabbits with cavitary tuberculosis produced no statistically significant effects. Experiments with many more rabbits would be required to prove whether or not such immunotherapy is beneficial.