Pilot licensing after aortic valve surgery.

Background and aim of the study: Bicuspid aortic valve is the most common congenital heart malformation, and a high percentage of patients with this condition will develop complications over time. It is rare that pilots undergo aortic valve surgery, and the confirmation of flight-licensing requirements after aortic valve replacement (AVR) is a challenge for the patient's cardiac surgeon and, particularly, for the Aeromedical Examiner (AME). Only AMEs are able to determine the flight status of pilots. Furthermore, in military and in civil aviation (e.g., Red Bull Air Race), the high G-load environment experienced by pilots is an exceptional physiological parameter, which must be considered postoperatively. Methods: A review was conducted of the aeronautical, surgical and medical literature, and of European pilot-licensing regulations. Case studies are also reported for two Swiss Air Force pilots. Results: According to European legislation, pilots can return to flight duty from the sixth postoperative month, with the following limitations: that an aortic bioprosthesis presents no restrictions in cardiac function, requires no cardioactive medications, yet requires a flight operation with co-pilot, the avoidance of accelerations over +3 Gz and, in military aviation, restricts the pilot to non-ejection-seat aircraft. The patient follow up must include both echocardiographic and rhythm assessments every six months. Mechanical prostheses cannot be certified because the required anticoagulation therapy is a disqualifying condition for pilot licensing. Conclusion: Pilot licensing after aortic valve surgery is possible, but with restrictions. The +Gz exposition is of concern in both military and civilian aviation (aerobatics). The choice of bioprosthesis type and size is determinant. Pericardial and stentless valves seem to show better flow characteristics under high-output conditions. Repetitive cardiological controls are mandatory for the early assessment of structural valve disease and rhythm disturbances. A pre-emptive timing is recommended when reoperation is indicated, without waiting for clinical manifestations of structural valve disease.

Differential regulations of AQP4 and Kir4.1 by triamcinolone acetonide and dexamethasone in the healthy and inflamed retina.

PURPOSE: Glucocorticoids are used to treat macular edema, although the mechanisms underlying this effect remain largely unknown. The authors have evaluated in the normal and endotoxin-induced uveitis (EIU) rats, the effects of dexamethasone (dex) and triamcinolone acetonide (TA) on potassium channel Kir4.1 and aquaporin-4 (AQP4), the two main retinal Müller glial (RMG) channels controlling retinal fluid movement. METHODS: Clinical as well as relatively low doses of dex and TA were injected in the vitreous of normal rats to evaluate their influence on Kir4.1 and AQP4 expression 24 hours later. The dose-dependent effects of the two glucocorticoids were investigated using rat neuroretinal organotypic cultures. EIU was induced by footpad lipopolysaccharide injection, without or with 100 nM intraocular dex or TA. Glucocorticoid receptor and channel expression levels were measured by quantitative PCR, Western blot, and immunohistochemistry. RESULTS: The authors found that dex and TA exert distinct and specific channel regulations at 24 hours after intravitreous injection. Dex selectively upregulated Kir4.1 (not AQP4) in healthy and inflamed retinas, whereas TA induced AQP4 (not Kir4.1) downregulation in normal retina and upregulation in EIU. The lower concentration (100 nM) efficiently regulated the channels. Moreover, in EIU, an inflammatory condition, the glucocorticoid receptor was downregulated in the retina, which was prevented by intravitreous injections of the low concentration of dex or TA. CONCLUSIONS: The results show that dex and TA are far from being equivalent to modulate RMG channels. Furthermore, the authors suggest that low doses of glucocorticoids may have antiedematous effects on the retina with reduced toxicity.

Peroxisome proliferator-activated receptor gamma and regulations by the ubiquitin-proteasome system in pancreatic cancer.

Pancreatic cancer is one of the most lethal forms of human cancer. Although progress in oncology has improved outcomes in many forms of cancer, little progress has been made in pancreatic carcinoma and the prognosis of this malignancy remains grim. Several molecular abnormalities often present in pancreatic cancer have been defined and include mutations in K-ras, p53, p16, and DPC4 genes. Nuclear receptor Peroxisome Proliferator-Activated Receptor gamma (PPARγ) has a role in many carcinomas and has been found to be overexpressed in pancreatic cancer. It plays generally a tumor suppressor role antagonizing proteins promoting carcinogenesis such as NF-κB and TGFβ. Regulation of pathways involved in pancreatic carcinogenesis is effectuated by the Ubiquitin Proteasome System (UPS). This paper will examine PPARγ in pancreatic cancer, the regulation of this nuclear receptor by the UPS, and their relationship to other pathways important in pancreatic carcinogenesis.

RXR: from partnership to leadership in metabolic regulations.

Vitamin A signaling occurs through nuclear receptors recognizing diverse forms of retinoic acid (RA). The retinoic acid receptors (RARs) bind all-trans RA and its 9-cis isomer (9-cis RA). They convey most of the activity of RA, particularly during embryogenesis. The second subset of receptors, the rexinoid receptors (RXRs), binds 9-cis RA only. However, RXRs are obligatory DNA-binding partners for a number of nuclear receptors, broadening the spectrum of their biological activity to the corresponding nuclear receptor-signaling pathways. The present chapter more particularly focuses on RXR-containing transcriptional complexes for which RXR is not only a structural component necessary for DNA binding but also acts as a ligand-activated partner. After positioning RXR among the nuclear receptor superfamily in the first part, we will give an overview of three major signaling pathways involved in metabolism, which are sensitive to RXR activation: LXR:RXR, FXR:RXR, and PPAR:RXR. The third and last part is focused on RXR signaling and its potential role in metabolic regulation. Indeed, while the nature of the endogenous ligand for RXR is still in question, as we will discuss herein, a better understanding of RXR activities is necessary to envisage the potential therapeutic applications of synthetic RXR ligands.

The effect of patient, provider and financing regulations on the intensity of ambulatory physical therapy episodes : a multilevel analysis based on routinely available data

Background: Many studies have found considerable variations in the resource intensity of physical therapy episodes. Although they have identified several patient-and provider-related factors, few studies have examined their relative explanatory power. We sought to quantify the contribution of patients and providers to these differences and examine how effective Swiss regulations are (nine-session ceiling per prescription and bonus for first treatments). Methods: Our sample consisted of 87,866 first physical therapy episodes performed by 3,365 physiotherapists based on referrals by 6,131 physicians. We modeled the number of visits per episode using a multilevel log linear regression with crossed random effects for physiotherapists and physicians and with fixed effects for cantons. The three-level explanatory variables were patient, physiotherapist and physician characteristics. Results: The median number of sessions was nine (interquartile range 6-13). Physical therapy use increased with age, women, higher health care costs, lower deductibles, surgery and specific conditions. Use rose with the share of nine-session episodes among physiotherapists or physicians, but fell with the share of new treatments. Geographical area had no influence. Most of the variance was explained at the patient level, but the available factors explained only 4% thereof. Physiotherapists and physicians explained only 6% and 5% respectively of the variance, although the available factors explained most of this variance. Regulations were the most powerful factors. Conclusion: Against the backdrop of abundant physical therapy supply, Swiss financial regulations did not restrict utilization. Given that patient-related factors explained most of the variance, this group should be subject to closer scrutiny. Moreover, further research is needed on the determinants of patient demand.

Mating triggers dynamic immune regulations in wood ant queens.

Mating can affect female immunity in multiple ways. On the one hand, the immune system may be activated by pathogens transmitted during mating, sperm and seminal proteins, or wounds inflicted by males. On the other hand, immune defences may also be down-regulated to reallocate resources to reproduction. Ants are interesting models to study post-mating immune regulation because queens mate early in life, store sperm for many years, and use it until their death many years later, while males typically die after mating. This long-term commitment between queens and their mates limits the opportunity for sexual conflict but raises the new constraint of long-term sperm survival. In this study, we examine experimentally the effect of mating on immunity in wood ant queens. Specifically, we compared the phenoloxidase and antibacterial activities of mated and virgin Formica paralugubris queens. Queens had reduced levels of active phenoloxidase after mating, but elevated antibacterial activity 7 days after mating. These results indicate that the process of mating, dealation and ovary activation triggers dynamic patterns of immune regulation in ant queens that probably reflect functional responses to mating and pathogen exposure that are independent of sexual conflict.