Search

The space environment is incredibly hostile, and humans are vulnerable in such conditions. Astronauts encounter various stress factors during a space journey, including radiation, microgravity, forceful acceleration during launch, altered magnetic fields, and confinement. These stressors significantly impact the human body homeostasis, leading to physio-pathological adaptations, loss of bone density, muscle atrophy, cardiovascular deconditioning, alterations in liver function, vestibular adaptations, and immune system dysregulation. These alterations can potentially influence drug pharmacokinetics and pharmacodynamics, affecting the efficacy and safety of medications administered to astronauts. Due to the limited number of studies on pharmaceuticals conducted in microgravity conditions, it’s challenging to assess the effectiveness and stability of these medications during spaceflight. The objective of the present work is to compare the state-of-the-art knowledge on PK/PD changes and factors likely to affect them during spaceflight, with the subjective perception of the problem by a collection of separate interviews conducted with seven experts in the field. The interviewees were chosen as “experts,” i.e., representatives in a specific discipline, who possess knowledge and experience in space pharmacology, physiology, or biology. Thus, our panel included astronauts, space surgeons, and scientists aiming to bridge the lack of experimental data in the literature. Each interview explores assorted aspects of space physiology and pharmacology, including drug use and storage onboard the ISS; notable consideration has arisen regarding the current research gaps and future space expeditions. All the interviews were held remotely using online conferencing software. None of the interviewees could provide a comprehensive overview regarding potential changes in drugs PK/PD in microgravity conditions. Further, any medication brought on board (whether as part of an astronaut’s medical kit or stored in the ISS pharmacy) is destroyed, thereby suppressing the possibility of analyzing any degradation products resulting from long-term exposure to microgravity and radiation. According to these results, the use of drugs without understanding how they are genuinely absorbed, distributed, metabolized, and excreted in microgravity conditions is concerning, posing risks for drug effectiveness. Conducting genotyping and phenotyping on astronauts would be beneficial for developing personalized pharmacological countermeasures for each astronaut and anticipating expected drug metabolism changes during space missions.

It is surprisingly difficult to notice when important information is missing (omission neglect) and yet, social media, advertisements, and other forms of communication typically only include one-sided information or positive attributes and omit opposing views or negative attributes. Even though it is surprisingly difficult to overcome this natural tendency, there are circumstances when decision makers are more sensitive to omissions. Understanding how and when decision makers can overcome this omission neglect tendency can be helpful to improve decision making in many situations. This paper investigates positive affect as a potential factor that can elicit sensitivity to omissions and alert decision makers to the need for additional information when important information is, in fact, missing. Four experiments use a consumer product choice situation to show that when decision makers are making an important decision, positive affect increases the likelihood that they will report a greater desire for additional product information (experiments 3 and 4) and temper their purchase interest in the target product. These results are shown using inference (experiments 1, 2, and 3) and by explicitly comparing a product choice with full and partial information (experiment 4). The results are discussed in terms of omission neglect literature as well as implications of the results for understanding the role of positive affect in information processing, judgment, and decision-making. These findings have implications for policy makers, marketers and others who are interested in message processing.

Children with celiac disease may face challenges in managing a gluten-free diet during their daily interactions and activities. The objective of this study was to compare how children with celiac disease manage their gluten-free diet and participate in food-related activities in Italy and Israel and to assess their quality of life. The previously validated Children’s Activities Report (CD-Chart) and the Disease-specific Health-Related Quality of Life Questionnaire for Children with Celiac Disease (CDDUX) were administered in Italy to children aged 8–16 diagnosed with CD (n = 39). The results were compared to data that had been previously gathered from Israeli children with CD (n = 106). The CD-Chart demonstrated satisfactory internal reliability within each cultural group (Italy: α = 0.82; Israel: α = 0.76). Mann–Whitney U-tests indicated significant differences between the two groups. The Italian children exhibited a significantly higher preference for participating in the activities compared to the Israelis (U = 3283.50, p < 0.001). Nonetheless, the Italian children displayed a notable decrease in their level of involvement in the preparation required before engaging in different activities (U = 760.50, p < 0.001). Moreover, they exhibited significantly lower self-determination in this preparatory process compared to the Israeli children (U = 726.00, p < 0.001). Significant group differences were found between the CDDUX children’s self-reports and parents’ proxy reports in the Israeli group but not in the Italian group. The CD-Chart revealed both shared and distinct participation characteristics in daily food-related activities across different cultural contexts. By incorporating the CD-Chart and the CDDUX, healthcare professionals can emphasize crucial aspects of day-to-day health management and guide them in establishing suitable intervention objectives to enhance effective health self-management.

PurposeCardiac involvement in Systemic Sclerosis (SSc) is increasingly recognized as a mayor cause of morbidity and mortality. The aim of present study is to investigate the early stages of cardiac involvement in SSc by Cardiovascular magnetic resonance (CMR), combining the non-invasive detection of myocardial inflammation and fibrosis using T2 and T1 mapping techniques and the assessment of microcirculatory impairment through perfusion response to cold pressor test (CPT).Methods40 SSc patients (30 females, mean age: 42.1 years) without cardiac symptoms and 10 controls underwent CMR at 1.5 T unit. CMR protocol included: native and contrast-enhanced T1 mapping, T2 mapping, T2-weighted, cineMR and late gadolinium enhancement (LGE) imaging. Microvascular function was evaluated by comparing myocardial blood flow (MBF) on perfusion imaging acquired at rest and after CPT. Native myocardial T1 and T2 relaxation times, extracellular volume fraction (ECV), T2 signal intensity ratio, biventricular volumes and LGE were assessed in each patient.ResultsSSc patients had significantly higher mean myocardial T1 (1029±32ms vs. 985±18ms, pConclusionsMyocardial involvement in SSc at preclinical stage increases native T1, T2 and ECV values, reflecting inflammation and fibrosis, and reduces vasodilatory response to CPT, as expression of microvascular dysfunction.

Many studies have demonstrated an association between diffuse bilateral testicular microlithiasis (TM) and gonadal and extragonadal germ cell tumors. Nevertheless, it is still uncertain whether ultrasound surveillance is really necessary in patients with TM in the absence of other risk factors such as previous testicular cancer, a history of cryptorchidism or testicular atrophy. We report the cases of a 33- and a 39-year-old man presenting with a retroperitoneal extragonadal tumor. The first patient underwent an MRI examination in order to rule out a lumbosacral hernia: MRI images showed no slipped disks but a voluminous retroperitoneal solid mass. The histological analysis revealed an immature teratoma. The second patient came to the emergency department complaining of abdominal pain, vomiting, weight loss and mild jaundice: ultrasound examination showed a large, ill-defined heterogeneous abdominal mass, confirmed by CT and MRI examination. The histology diagnosed a yolk sac tumor. In both patients, the testicular sonography was performed to rule out a focal lesion, but it displayed bilateral TM without a focal testicular mass. Based on our direct experience, we highlight the importance of annual ultrasonographic surveillance of the testis and the retroperitoneal space in patients with occasionally detected TM.

This paper shows the results of the monitoring carried out in three hilly farms of the MONACO project in order to verify the effectiveness of the Standard 1.1 (commitment a) (temporary ditches) and Standard 1.2 (commitment g) (Vegetation cover throughout the year in set-aside land) in the reduction in soil erosion, contained in Rule 1: ‘minimum land management that meets specific conditions’ of the decree Mipaaf 2009 and following modifications, until the recent decree No. 180 of January 23, 2015. In addition, the assessment of the competitiveness gap was done. That is the evaluation of the additional costs borne by the beneficiary of the single payment determined from agronomic commitments. Monitoring has also compared the erosion actually observed in the field with that predicted by RUSLE model (Revised Universal Soil Loss Equation) (Renard et al., 1997) in the two situations: with and without the presence of temporary ditches, i.e. assuming Factual (compliance rules) and in that Counterfactual (infringement). This comparison was made in view of the fact that the RUSLE model was chosen by the 'European Evaluation Network for Rural Development (EEN, 2013) as a forecasting tool for the quantification of' Common Indicator ‘soil erosion by water’. The results of soil erosion survey carried out by using a new UAV-GIS methodology on two monitoring farms in two years of observations have shown that temporary ditches were effective in decreasing erosion, on average, by 42.5%, from 36. 59 t ha-1 to 21.05 t ha-1 during the monitoring period. It was also evaluated the effectiveness of grass strips (at variance with the commitment of temporary ditches). The results showed a strong, highly significant, reduction in erosion by about 35% times respect soil erosion observed in bare soil and also a significant reduction in the volume of runoff water. With regard to Standard 1.2 (commitment g) the statistical analysis shows a strong and highly significant decrease in the erosion due to the vegetation cover of the soil compared to bare soil. The economic competitiveness gap of Standard 1.1(commitment a) stood at € 4.07±1.42 € ha-1 year-1, while CO2 emissions due to execution of temporary ditches was 2.58 kg ha-1year-1. As for the Standard 1.2 (commitment g) the average differential competitiveness gap amounted to 50.22±13.7 € ha-1 year-1 and an output of CO2 equal to 31.52 kg ha-1 year.

PIK3CA upregulation, amplification and mutation have been widely reported in ovarian cancers and other tumors, which strongly suggests that PIK3CA is a promising therapeutic target. However, to date the mechanisms underlying PIK3CA regulation and activation in vivo is still unclear. During tumorigenesis, host-tumor interactions may play a critical role in editing the tumor. Here, we report a novel mechanism through which the tumor microenvironment activates the PIK3CA oncogene. We show that PIK3CA upregulation occurs in non-proliferating tumor regions in vivo. We identified and characterized the PIK3CA 5' upstream transcriptional regulatory region and confirmed that PIK3CA is transcriptionally regulated through NF-kappaB pathway. These results offer a new mechanism through which the tumor microenvironment directly activates oncogenic pathways in tumor cells.

OBJECTIVE: The aim of this study was to evaluate the accuracy of unenhanced whole-body MRI, including whole-body Diffusion Weighted Imaging (DWI), used as a diagnostic modality to detect pathologic lymph nodes and skeletal metastases in patients with prostate cancer (PCa) undergoing restaging after primary treatment. PATIENTS AND METHODS: 152 male patients with biochemical recurrence after radical prostatectomy (RP) or external beam radiation therapy (EBRT) underwent MRI at a 1.5 Tesla magnet with whole spinal sagittal T2-weighted, sagittal T1- weighted, sagittal STIR images, axial T1 and T2- weighted and STIR images of the pelvis and whole-body. 18Fcholine-PET/CT exam was used as the reference standard. RESULTS: MRI protocol including whole-body combined T1-weighted+T2-weighted+STIR+DWI showed a sensitivity (Se) of 99%, a specificity (Spe) of 98%, a positive predictive value (PPV) of 98%, a negative predictive value (NPV) of 96%, an accuracy of 98% and an area under the receiver operating characteristic curve (AUC) of 0.971 for identification of bone metastatic lesion. The same protocol, displayed a Se of 98%, a Spe of 99%, a PPV of 97%, a NPV of 98%, an accuracy of 98 % and an AUC of 0.960 in the detection of pathologic lymph nodes. CONCLUSIONS: Unenhanced whole-body MRI, including whole-body-DWI, is an accurate and cost-effective diagnostic tool which is able to detect lymph node involvement and bone metastases in patients with biochemically recurrent PCa after RP or EBRT. Thanks to its lack of ionizing radiation, excellent soft tissue contrast, high spatial resolution, no need of contrast agent, high Se and Spe, it could play a role in the restaging procedure of such patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to evaluate the clinical usefulness of computed tomography colonography (CTC) in the preoperative staging in patients with abdominal pain for occlusive colorectal cancer (CRC) and to compare the results of CTC with the surgical ones. PATIENTS AND METHODS: 127 patients with abdominal pain, iron deficiency anemia and occlusive CRC underwent a CTC examination in prone position without intravenous contrast agent and in prone position after administration of intravenous contrast medium. All the patients underwent surgery after CTC. Two radiologists with different experience analyzed the images first independently and then by consensus. They evaluated the location of the lesion, the depth of the invasion of the colon-rectal wall (T stage), lymph node involvement (N stage) and the presence or absence of distant metastasis (M stage). CTC findings were correlated with surgical outcomes. RESULTS: The overall accuracy values for tumour localization according to consensus reading of CTC examinations in comparison to surgical results were 100% (K = 1, p = 0.0001). The overall accuracy values of agreement for T staging of reader 1, reader 2 and consensus reading of CTC examinations in comparison to surgical results were respectively 95.5% (K = 0.876, p = 0.0035), 93.3% (K = 0.858, p = 0.0037) and 97.7% (K = 0.926, p = 0.0014) for = = T2; 91.3% (K = 0.839, p = 0.0027), 88.3% (K = 0.817, p = 0.0031), and 92.9% (K = 0.894, p = 0.0025) for T3; 89.6% (K = 0.825, p = 0.0037), 86.2% (K = 0.837, p = 0.0032) and 89.6% (K = 0.821, p = 0.0023) for T4. The overall accuracy values for N staging for reader 1, reader 2 and consensus reading was 90.2% (K = 0.865, p = 0.0029). The overall accuracy values for M staging of reader 1, reader 2 and consensus reading was 92% (K = 0.875, p = 0.0019). CONCLUSIONS: CTC with is a very useful tool for accurate pre-treatment staging and localization of occlusive CRC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study is to prove if dynamic HASTE (half-Fourier acquisition single-shot turbo spin-echo) sequences can be used in the diagnosis of internal derangement disorders of temporomandibular joint (TMJ) as an alternative to static proton density (PD) weighted/turbo spin echo (TSE) T2-weighted sequences which are considered up to now as the gold standard in the evaluation of TMJ disorders (TMDs). PATIENTS AND METHODS: 194 patients for a total of 388TMJs were examined with a 1.5Tesla field strength superconducting magnet. Sagittal static PD-weighted/TSE T2-weighted and dynamic HASTE sequences have been used. Three experts in the field of oral radiology (specialist A, B and C) independently and blinded to clinical symptoms and any treatment, assessed the articular disc position in each TMJ (rated as normal or disc displacement with reduction or disc displacement without reduction). The agreement between static and dynamic images and between the three different specialists in the assessment of the articular disc position was evaluated using kappa statistic. RESULTS: The agreement between static and dynamic images is: for specialist A, K = 0.862; for specialist B, K = 0.870 and for specialist C, K = 0.862. CONCLUSIONS: Since there is no complete agreement between these two MR techniques, dynamic sequences can not be used as a reliable alternative to static sequences in the evaluation of internal derangement disorders of TMJ. [ABSTRACT FROM AUTHOR]

PURPOSE: To assess bone density of kneecaps in subjects with femoro-tibial prothesis before and after surgery by means of DEXA examination. SUBJECTS AND METHODS: We examined 34 patients with unilateral femoro-tibial prosthesis, 20 healthy subjects of the same age and non-carriers of knee replacement and 14 healthy young adult subjects. All the data sets were analysed by two radiologists (AS and AM). The coincidence of the results between the two specialists was evaluated by means of Cohen's Kappa index and the results were considered statistically significative if p value is < of 0.05. RESULTS: The values of patellar BMD in the group of 34 patients, were: a minimum of 0.386 g/cm² (K = 0.879, p = 0.0012), a maximum 1.707 g/cm² (K = 0.886, p = 0.0016). The comparison between the left and right knee showed the following data: minimum difference 0.034 g/cm² (K = 0.901, p = 0.0015), maximum difference of 0.622 g/cm² (K = 0.908, p = 0.0017), the average was found to be of 0.277 g/cm² (K = 0.894, p = 0.0018). But this difference tends to decrease 6 months after surgery. In the group of healthy young adults, we obtained the following values: a minimum of 0.782 g/cm² (K = 0.907, p = 0.0025), maximum 1.503 g/cm² (K = 0.932, p = 0.0012). Between both knees, the difference was minimal 0.006 g/cm² (K = 0.951, p = 0.0035) and maximum 0.096 g/cm² (K = 0.926, p = 0.0007) with an average difference of 0.058 g/cm² (K = 0.954, p = 0.0026). In the group of healthy subjects of the same age and non-carriers of knee replacement the values were average higher. A maximum value of 1.134 g/cm² (K = 0.894, p = 0.0028) and a minimum value of 0.944 g/cm² (K = 0.892, p = 0.0023) were found; between both knees a minimum difference of 0.010 g/cm² (K = 0.918, p = 0.0047) and a maximum of 0.090 g/cm² (K = 0.937, p = 0.0017) were found, with an average difference of 0.052 g/cm² (K = 0.956, p = 0.0024). CONCLUSIONS: DEXA examination of the patellar is recommended as a supplementary study to the clinical and radiological standard exams because it is able to provide additional information to determine when to intervene surgically, on the basis of patellar bone density values. [ABSTRACT FROM AUTHOR]