Mechanobiology of the relocation of proteins in advecting cells: in vitro experiments, multi-physics modeling, and simulations.

Cell motility-a cellular behavior of paramount relevance in embryonic development, immunological response, metastasis, or angiogenesis-demands a mechanical deformation of the cell membrane and influences the surface motion of molecules and their biochemical interactions. In this work, we develop a fully coupled multi-physics model able to capture and predict the protein flow on endothelial advecting plasma membranes. The model has been validated against co-designed in vitro experiments. The complete picture of the receptor dynamics has been understood, and limiting factors have been identified together with the laws that regulate receptor polarization. This computational approach might be insightful in the prediction of endothelial cell behavior in different tumoral environments, circumventing the time-consuming and expensive empirical characterization of each tumor.

Triage in military settings.

Triage, a medical term derived from the French word "trier", is the practical process of sorting casualties to rationally allocate limited resources. In combat settings with limited medical resources and long transportation times, triage is challenging since the objectives are to avoid overcrowding medical treatment facilities while saving a maximum of soldiers and to get as many of them back into action as possible. The new face of modern warfare, asymmetric and non-conventional, has led to the integrative evolution of triage into the theatre of operations. This article defines different triage scores and algorithms currently implemented in military settings. The discrepancies associated with these military triage systems are highlighted. The assessment of combat casualty severity requires several scores and each nation adopts different systems for triage on the battlefield with the same aim of quickly identifying those combat casualties requiring lifesaving and damage control resuscitation procedures. Other areas of interest for triage in military settings are discussed, including predicting the need for massive transfusion, haemodynamic parameters and ultrasound exploration.

Leptin level lowers in proportion to the amount of aerobic work after four weeks of training in obesity.

Leptin values are higher in obesity. Physical exercise reduces fat mass (FM) and decreases leptin levels. Intensity of physical training seems to play a role in reducing circulating leptin. In 16 obese subjects (8 men and 8 women, age 38.6±3.9 years, BMI 35.9±1.8 kg/m(2)), leptin was sampled before and after 4 weeks of controlled training. Eight subjects (4 men and 4 women) performed an aerobic training schedule (Group A), the remainders an aerobic training program with a bout of work beyond the anaerobic threshold (AT) (Group B). Training determined a reduction in leptin levels in both groups, which was significant in Group A (12.2 vs. 27.8 µg/l, p<0.05), even when related to the change in FM (0.372 vs. 0.762 µg/l/kg, p<0.05). FM decreased significantly in Group B when compared to Group A (-7.4 vs. -2.6 kg, respectively, p<0.001). While in Group A the slight loss of FM was aggregated to a significant decrease in leptin levels, the opposite occurred in Group B. In Group A, leptin lowering was proportional to the amount of total work performed (p<0.001, R(2)=0.89). In obesity, a reduction is observed in leptin levels after short-term training, which is seemingly dissociated from concomitant decrease of FM. Aerobic training alone appears to be linked to a greater leptin reduction, which is well correlated with the amount of work performed.

Acute post-exercise oxygen uptake, hormone and plasma metabolite response in obese men.

This study aimed to compare oxygen uptake ( VO2), hormone and plasma metabolite responses during the 30 min after submaximal incremental exercise (Incr) performed at the same relative/absolute exercise intensity and duration in lean (L) and obese (O) men. Eight L and 8 O men (BMI: 22.9 ± 0.4; 37.2 ± 1.8 kg · m(-2)) completed Incr and were then seated for 30 min. VO2 was monitored during the first 10 min and from the 25-30(th) minutes of recovery. Blood samples were drawn for the determination of hormone (catecholamines, insulin) and plasma metabolite (NEFA, glycerol) concentrations. Excess post-exercise oxygen consumption (EPOC) magnitude during the first 10 min was similar in O and in L (3.5 ± 0.4; 3.4 ± 0.3 liters, respectively, p=0.86). When normalized to percent change ( VO2END=100%), % VO2END during recovery was significantly higher from 90-120 s in O than in L (p ≤ 0.04). There were no significant differences in catecholamines (p ≥ 0.24), whereas insulin was significantly higher in O than in L during recovery (p=0.01). The time-course of glycerol was similar from 10-30 min of recovery (-42% for L; -41% for O, p=0.85), whereas significantly different patterns of NEFA were found from 10-30 min of recovery between groups (-18% for L; +8% for O, p=0.03). Despite similar EPOC, a difference in VO2 modulation between groups was observed, likely due to faster initial rates of VO2 decline in L than in O. The different patterns of NEFA between groups may suggest a lower NEFA reesterification during recovery in O, which was not involved in the rapid EPOC component.

Mass loads of dissolved and particulate mercury and other trace elements in the Mt. Amiata mining district, Southern Tuscany (Italy).

Total dissolved and particulate mercury (Hg), arsenic (As), and antimony (Sb) mass loads were estimated in different seasons (March and September 2011 and March 2012) in the Paglia River basin (PRB) (central Italy). The Paglia River drains the Mt. Amiata Hg district, one of the largest Hg-rich regions worldwide. Quantification of Hg, As, and Sb mass loads in this watershed allowed (1) identification of the contamination sources, (2) evaluation of the effects of Hg on the environment, and (3) determination of processes affecting Hg transport. The dominant source of Hg in the Paglia River is runoff from Hg mines in the Mt. Amiata region. The maximum Hg mass load was found to be related to runoff from the inactive Abbadia San Salvatore Mine (ASSM), and up to 30 g day(-1) of Hg, dominantly in the particulate form, was transported both in high and low flow conditions in 2011. In addition, enrichment factors (EFs) calculated for suspended particulate matter (SPM) were similar in different seasons indicating that water discharge controls the quantities of Hg transported in the PRB, and considerable Hg was transported in all seasons studied. Overall, as much as 11 kg of Hg are discharged annually in the PRB and this Hg is transported downstream to the Tiber River, and eventually to the Mediterranean Sea. Similar to Hg, maximum mass loads for As and Sb were found in March 2011, when as much as 190 g day(-1) each of As and Sb were measured from sites downstream from the ASSM. Therefore, the Paglia River represents a significant source of Hg, Sb, and As to the Mediterranean Sea.

Rationale for hospital-based rehabilitation in obesity with comorbidities.

Severely obese patients affected by two or more chronic conditions which could mutually influence their outcome and disability can be defined as "complex" patients. The presence of multiple comorbidities often represents an obstacle for being admitted to clinical settings for the treatment of metabolic diseases. On the other hand, clinical Units with optimal standards for the treatment of pathological conditions in normal-weight patients are often structurally and technologically inadequate for the care of patients with extreme obesity. The aims of this review paper were to review the intrinsic (anthropometrics, body composition) and extrinsic (comorbidities) determinants of disability in obese patients and to provide an up-to-date definition of hospital-based multidisciplinary rehabilitation programs for severely obese patients with comorbidities. Rehabilitation of such patients require a here-and-now multidimensional, comprehensive approach, where the intensity of rehabilitative treatments depends on the disability level and severity of comorbidities and consists of the simultaneous provision of physiotherapy, diet and nutritional support, psychological counselling, adapted physical activity, specific nursing in hospitals with appropriate organizational and structural competences.

[Labour epidural analgesia for a parturient with a factor XI deficiency: an ill-considered challenge or a reasonable risk?]. / Analgésie péridurale obstétricale chez une parturiente atteinte d'un déficit en facteur XI : défi inconsidéré ou risque raisonné ?

The authors report the performance of a labour epidural analgesia in a 26-year-old parturient presenting a moderate factor XI (FXI) deficiency. If haemostasis disorders usually contraindicate an epidural analgesia (with a risk of epidural haematoma), a moderate FXI deficiency is not an absolute contraindication to perform such an epidural analgesia. Desmopressin, sometimes used in surgery to reduce the bleeding, was administered to withdraw the catheter in better haemostasis conditions. No neurological signs were observed.

QT prolongation in anaesthetized guinea-pigs: an experimental approach for preliminary screening of torsadogenicity of drugs and drug candidates.

Many non-cardiovascular drugs can prolong the QT interval of the electrocardiogram (ECG); this is an accessory property not necessary for their pharmacological action and generally linked to the block of the potassium HERG channels and delayed cardiac repolarization. The QT prolongation can lead to a dangerous tachyarrhythmia, called torsade de pointes, and potentially to fatal ventricular fibrillation. The experimental approaches, aimed at an early identification of this undesidered property, often require sophisticated and expensive equipment or the use of superior animal species (dog, primates) that cannot be employed easily for ethical and/or economic reasons. This work aimed to study drug-induced QT prolongation in anaesthetized guinea-pigs and to evaluate the reliability of such an experimental approach to obtain a satisfying predictive parameter of the torsadogenicity of drugs in humans. Seven drugs that were torsadogenic in humans (astemizole, cisapride, haloperidol, quinidine, sotalol, terfenadine and thioridazine) and two that were non-torsadogenic (chlorprotixene and diazepam) were administered i.v. to guinea-pigs under pentobarbital anaesthesia. The ECGs were recorded by four electrodes inserted in the subcutaneous layer of the limbs. Both RR and QT intervals were measured in Leads II and III and then the correct QT values were calculated by Bazett and Fridericia algorithms (QTcB and QTcF, respectively). All the drugs, with the exception of chlorprotixene and diazepam, produced a dose-dependent prolongation of the QT and RR intervals and a significant increase of QTcB and QTcF values. It can be concluded that this method represents a rapid and low-cost procedure to evaluate the cardiac safety pro fi le in the preliminary screening of a high number of drugs or drug candidates.

Neonatal respiratory morbidity risk and mode of delivery at term: influence of timing of elective caesarean delivery.

AIM: To establish whether the timing of delivery between 37 + 0 and 41 + 6 wk gestation influences neonatal respiratory outcome in elective caesarean delivery, following uncomplicated pregnancy, thus providing information that can be used to aid planning of elective delivery at term. METHODS: All pregnant women who were delivered by elective caesarean delivery at term during a 3-y period were identified from a perinatal database and compared retrospectively with pregnant women matched for week of gestation, who were vaginally delivered. Maternal characteristics, neonatal outcome, incidence of respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN) were analysed. During this time, 1284 elective caesarean section deliveries occurred at or after 37 + 0 wk of gestation. RESULTS: Neonatal respiratory morbidity risk (odds ratio, OR), including RDS and TTN, was significantly higher in the infant group delivered by elective caesarean delivery compared with vaginal delivery (OR 2.6; 95% CI: 1.35-5.9; p < 0.01). While TTN risk in caesarean delivery was not increased (OR 1.19; 95% CI: 0.58-2.4; p > 0.05), the RDS risk was significantly increased (OR 5.85; 95% CI: 2.27-32.4; p < 0.01). This RDS risk is greatly increased in weeks 37 + 0 to 38 + 6 (OR 12.9; 95% CI: 3.57-35.53; p < 0.01). After 39 + 0 wk, there was no significant difference in RDS risk. CONCLUSIONS: Infants born by elective caesarean delivery at term are at increased risk for developing respiratory disorders compared with those born by vaginal delivery. A significant reduction in neonatal RDS would be obtained if elective caesarean delivery were performed after 39 + 0 gestational weeks of pregnancy.

Effects of intravitreal indocyanine green injection in rabbits.

PURPOSE: To report the clinical, electrophysiologic, and histologic findings of different concentrations of indocyanine green (ICG) injected into the vitreous cavity of rabbit eyes. METHODS: Forty-two rabbits underwent intravitreal injection of 0.1 mL of ICG in three different concentrations: 0.5 mg/mL (250 mOsm), 5 mg/mL (270 mOsm), and 25 mg/mL (170 mOsm). Fellow eyes were injected with 0.1 mL of balanced salt solution. Biomicroscopy, ophthalmoscopy, electroretinography, fluorescein angiography, and histologic evaluation were performed. RESULTS: Eyes injected with 0.5 mg/mL of ICG showed b-wave latency delay on the first day after injection. Eyes injected with 5 mg/mL of ICG showed b-wave latency delay and decreased b-wave amplitude on the first and seventh days after injection; delayed a-wave latency on the first day after injection was also observed. Eyes injected with 25 mg/mL of ICG showed b- and a-wave amplitude and latency abnormalities during the entire follow-up. Direct correlation of increasing retinal edema proportional to the progressively increasing ICG concentrations was shown on histologic evaluation. CONCLUSION: Intravitreal ICG injection in rabbit eyes may impair retinal function and morphology proportional to the progressively increasing ICG dosages.

[Sentinel lymph nodes in cutaneous melanoma: the experience in the Florence area]. / Linfonodo sentinella nel melanoma cutaneo: l'esperienza nell'area fiorentina.

In the period 1997-2001, 466 sentinel lymph nodes from 342 lymphatic basins in 322 melanoma patients were examined at the Health Unit of Florence. The lymphatic mapping was performed through pre-operative lymphoscintigraphy using technetium-labelled nano-colloid, intradermal injections of vital blue dye and intra-operative gamma-probe. The examined patients were 182 females and 140 males. Sentinel lymph node was one in 65.2% of cases; two sentinel lymph nodes were detected in 27% of cases and more than 2 sentinel nodes were detected in 7.8% of cases. Melanoma metastases in one or more sentinel lymph nodes were found in 61/322 patients (18.9%). Lymphatic basins resulted to be involved by melanoma metastases were 64/342 (18.7%); sentinel lymph nodes containing metastatic melanoma deposits were 73/466 (15.6%). No metastasis was found in patients with melanoma thickness < or = 1 mm. One or more positive sentinel lymph nodes were found in 7.5% of patients with melanoma thickness > 1.00 and < or = 1.50 mm, in 27.7% of patients with melanoma > 1.50 and < or = 3.00 mm, in 38.2% of patients with melanoma > 3.00 and < or = 4.00, and in 60.7% of patients with melanoma > 4.00 mm. Frozen section analysis of sentinel lymph nodes, performed in 59/61 patients with nodal metastases, detected nodal involvement in 21 patients (35.6%). Metastases were identified by routine hematoxylin-eosin staining in 57/64 positive lymphatic basins; in 7 cases (11%) metastases were detected by immunohistochemical stainings (S100 and HMB-45). A nodal nevus was found in 3/466 sentinel lymph nodes (0.6%). Our data are analyzed and compared to previously data of the literature. The value of frozen section analysis and the major problems in the diagnosis of melanoma micrometastases in sentinel lymph nodes are discussed. The importance of the sentinel node biopsy for the detection of occult metastases and for the correct staging of melanoma patients are stressed, according to the new TNM melanoma classification.

Microsatellite analysis in cutaneous malignant melanoma.

The status and relevance of repetitive nucleotide sequences or microsatellite alterations in sporadic cutaneous melanoma has not been fully clarified. In this study we evaluated the presence of microsatellite alterations in a series of sporadic primary and metastatic melanomas in order to discover which genetic events may have a pathogenetic role in the development of this disease. Tumour samples were obtained from 21 patients with sporadic cutaneous melanoma, and from eight corresponding positive sentinel lymph nodes and one corresponding in-transit metastasis. In each specimen, selected neoplastic cells were procured by laser-assisted microdissection. Polymerase chain reaction-based microsatellite analysis was performed using a panel of 11 microsatellite markers, located at chromosome 2p, 4q, 9p, 16q, 17p and 21q. Overall, we found microsatellite alterations in five (23.8%) melanomas. Of these, one case showed alteration at marker D2S2182 and one at marker D17S261, whereas in another case alterations at three loci, D2S2182, D2S2291 and D9S171, were found. The fourth patient demonstrated an alteration at locus D9S171 both in the primary tumour and in the histologically positive sentinel lymph node. The fifth case was characterized by alterations at D2S2182 and at D17S250, whereas the corresponding in-transit metastasis showed the same alterations as the primary tumour and an additional alteration at IFN alpha. In conclusion, our study confirms previous observations that cutaneous melanomas demonstrate microsatellite alterations, although such instability occurs at a lower frequency than specific mismatch repair defects. Genetic analysis of metastatic lesions revealed that the same microsatellite alterations as in the primary tumour are seen, but additional genetic changes may develop during disease progression.

Carcinomas of sweat glands: report of 60 cases.

CONTEXT: Several aspects of sweat gland carcinomas (incidence, classification, diagnosis, and behavior) have not been definitively clarified and need to be studied further. OBJECTIVE: The clinicopathologic findings of a large series of sweat gland carcinomas, collected during a period of 15 years, are presented. METHODS: Sixty sweat gland carcinomas (41 porocarcinomas, 3 syringomatous carcinomas, 8 ductal carcinomas, 5 adenoid cystic carcinomas, and 3 mucinous carcinomas) were analyzed histologically and immunohistochemically. RESULTS: Porocarcinomas were composed of eosinophilic and clear atypical cells arranged in solid-cystic lobular masses. These tumors were divided into 2 subgroups: horizontal porocarcinomas, showing a prominent intraepidermal component, and nodular porocarcinomas, which demonstrated predominant nodular growth. Syringomatous carcinomas presented keratinizing and nonkeratinizing cysts, dilated tubules (sometimes with a "tadpole" appearance), small neoplastic ducts, solid islands, and cellular cords. Ductal carcinomas were characterized by a prominent formation of tubules, solid islands, and cellular cords. Adenoid cystic carcinomas presented a characteristic pattern, showing basaloid monomorphous cells with moderately atypical nuclei, arranged in cribriform or solid islands and in tubular structures. Mucinous carcinomas were composed of moderately atypical cells with eosinophilic vacuolated cytoplasm, forming solid and cystic islands floating in large mucin pools. Immunohistochemically, cytokeratin was found in neoplastic cells in all cases, carcinoembryonic antigen was detected in 73% of cases, and actin-positive (myoepithelial) cells were not found. CONCLUSIONS: Although numerous studies have been published in recent years, the histologic features, histogenesis, and classification of sweat gland carcinomas still remain controversial and need to be clarified by further studies.