The role of the perioperative prone position in the low recurrence of pressure injuries in the pelvic region.

OBJECTIVE: A pressure injury (PI) is a localised area of damage to the skin and/or underlying soft tissue as a result of a sustained mechanical loading. There are three key aetiological mechanisms to PI formation-direct cell deformation, inflammatory oedema and ischaemic damage-which are typically activated sequentially to drive a spiral of injury. This article discusses the role of the perioperative prone position as a rational approach to reducing the recurrence of pelvic PI after reconstructive surgery. METHOD: Patients with deep PI in the pelvic region, who were operated on from 2011 to 2019, were retrospectively evaluated. The protocol of care included training in the prone position, followed by maintenance of the prone position for 4-6 weeks postoperatively. The reconstruction was performed with fasciocutaneous and myocutaneous local or regional flaps. RESULTS: The study evaluated a total of 26 patients. The rate of recurrence of PIs was 15.4% (4/26) in the mean follow-up of 54 months. Regarding postoperative complications, four cases of partial dehiscence of the suture occurred. CONCLUSION: This perioperative protocol of maintaining a prone position seems to be safe for the patient, and it can be used to prevent or reduce the recurrence of deep PIs on the pelvic region after reconstructive surgery.

Agreement on the prescription of antimicrobial drugs.

BACKGROUND: There is universal awareness of the difficulties faced by doctors when prescribing antimicrobials. METHODS: Over a six-month period patients hospitalized in the ICU and under treatment with antibiotics and/or antifungals were eligible to participate in the study. The data were assessed by two infectious diseases specialists. Once completed, all case forms were sent independently to both evaluators (TZSC and ARM) by e-mail. Based on the data received, the evaluator completed a form automatically generated on the e-mail and returned it to the original mailbox for further analysis. We assessed the level of agreement between infectious disease specialists and the physicians directly responsible for the decision to begin antimicrobial therapy, as well as to assess the appropriateness of the regimen prescribed. RESULTS: Among the antimicrobial regimens prescribed to the 177 patients, 36% were considered inappropriate by specialist #1 and 38% were considered inappropriate by specialist #2. We found 78% agreement by at least one of the infectious disease specialists with the prescribed antimicrobial regimen, and in 49% of cases both specialists agreed with the prescribed regimen. Both disagreed with the prescribed regimen in 22% of the cases and they disagreed between themselves in 29% of the cases. CONCLUSION: This study highlights the difficulties in prescribing effective empirical antimicrobial therapy--they are of such magnitude that even two specialists in infectious diseases, well acquainted with our hospital's resistance patterns and our patients' profiles have considerable disagreement.

The impact of the COVID-19 pandemic on the use of diagnostic imaging examinations in the Brazilian unified healthcare system (SUS).

Objectives: To assess the impact of the COVID-19 pandemic on the volumes of use of diagnostic imaging examinations in the Brazilian Unified Health System (SUS), the only healthcare provider for approximately 160 million people. Methods: We collected the monthly numbers of diagnostic imaging examinations in the years 2019, 2020, and 2021 from a database provided by SUS. Data were collected by specific type of examination across different imaging modalities, both for the outpatient (elective and emergency) and inpatient settings. Results: There was a large reduction in the annual volume of almost all types of diagnostic imaging examinations in SUS in 2020, compared to 2019. Decreases were generally greater among outpatients than in the hospital setting, in which the annual volume of use of most modalities was similar or even higher in 2021 than in the pre-pandemic period. Computed tomography (CT) was the only modality for which use increased in 2020 compared to 2019. In contrast to other types of examinations, the use of chest CT was much higher in both 2020 and 2021 than in the preceding years. The relative changes in diagnostic imaging use in SUS started around March-April 2020, when the pandemic began to get worse in Brazil, and tended to correlate to COVID-19 incidence in Brazil over the following months. Conclusions: The COVID-19 pandemic had a large impact on the use of diagnostic imaging examinations in the SUS. Policies and actions are needed to alleviate the resulting potential adverse health effects and to optimize the use of diagnostic tests in the future.

Integrating X-ray kV millimetric field dosimetry with a synthetic diamond detector into the treatment planning system commissioning of a preclinical irradiator.

PURPOSE: Small animal irradiators are equipped with x-ray beams and cone collimators with millimeter dimensions to be used in preclinical research. The use of small fields in the kV energy range may require the application of energy-dependent, field size-dependent, or depth-dependent correction factors to the dosimetric data acquired for treatment planning system (TPS) commissioning purposes to obtain accurate dose values. Considering that these corrections are also detector dependent, the suitability of a synthetic single-crystal diamond detector for small-field relative dosimetry in a preclinical irradiator (220-kVp) was evaluated to avoid the necessity of applying correction factors during TPS commissioning. METHODS: The detector response was assessed during the transition for field sizes ranging from 20 × 20 mm2 to 3 × 3 mm2 , using the small animal radiation research platform (SARRP). The percentage depth dose distributions (PDDs), lateral profiles and output factors (OFs) were measured. The PDDs for the synthetic diamond detector were compared to the distributions acquired using a small-volume microchamber (0.016 cm3 ) and with Monte Carlo calculations using the MC3D in-house software package. The profiles and OFs were compared to the data from a silicon solid-state detector and to radiochromic film data provided by the manufacturer; for the OF determination, measurements made using a microchamber were added for comparison. The performance of several detectors used as references was previously validated for relative dosimetry in preclinical irradiators. A commercial TPS was commissioned for the factor-based algorithm, using the data acquired with the diamond detector, and no additional correction factors were applied. To verify the performance of the TPS and the accuracy of the dosimetric methodology, radiochromic film irradiation in water was conducted, and two-dimensional (2D) dose distributions in the coronal and axial planes were compared under different gamma criteria. RESULTS: Compared with the microchamber and MC3D distributions, the agreement of the PDDs using the synthetic diamond detector was better than 2%. The profile data exhibited very good agreement compared with the data from the silicon detector, with an average and a maximum difference of 0.31 and 0.39 mm in the penumbras, respectively. Compared with the data from the radiochromic film, the average and maximum differences were equal to 0.77 and 0.89 mm, respectively. Very good agreement, within 1%, was obtained between the OFs measured with the synthetic diamond detector and the radiochromic film, compared only for the cone collimators. The validation of the TPS commissioning using gamma criteria compared to film showed an average passing rate of 100% and 93.2% with a global gamma criterion of 1 mm/3% for the coronal and axial planes, respectively, including the 3 × 3 mm2 field size and penumbra regions. CONCLUSIONS: Synthetic diamond is a suitable detector for the complete relative dosimetry of small x-ray fields. The commissioning of the TPS with its own beam dosimetric data exhibited encouraging results even in a 3 × 3 mm2 field and penumbra region. This methodology allows for the prediction of 2D dose distributions with an accuracy in water ranging from 3 to 5% compared to the 2D distribution from film dosimetry.

Development, Characterization, and In Vivo Evaluation of a Novel Aptamer (Anti-MUC1/Y) for Breast Cancer Therapy.

MUC1, the transmembrane glycoprotein Mucin 1, is usually found to be overexpressed in a variety of epithelial cancers playing an important role in disease progression. MUC1 isoforms such as MUC1/Y, which lacks the entire variable number of tandem repeat region, are involved in oncogenic processes by enhancing tumour initiation. MUC1/Y is therefore considered a promising target for the identification and treatment of epithelial cancers; but so far, the precise role of MUC1/Y remains to be elucidated. In this work, we developed and identified a DNA aptamer that specifically recognizes the splice variant MUC1/Y for the first time. The DNA aptamer could bind to a wide variety of human cancer cells, and treatment of MUC1/Y positive cells resulted in reduced growth in vitro. Moreover, MUC1/Y aptamer inhibited the tumour growth of breast cancer cells in vivo. The present study highlights the importance of targeting MUC1/Y for cancer treatment and unravels the suitability of a DNA aptamer to act as a new therapeutic tool.

Small-field dosimetry with a high-resolution 3D scanning water phantom system for the small animal radiation research platform SARRP: a geometrical and quantitative study.

Improvements in dosimetry in preclinical radiation research facilitate the application of results to the newest radiotherapy techniques, reducing gaps that hinder translation. Currently, guidelines for small-field kV photon dosimetry of small animal irradiators have not been published, and most of the publications are based on radiochromic film dosimetry. In this study, we evaluated the performance of four detectors, three ionization chambers (ICs): (PTW Advanced Markus, PTW Semiflex 31010, PTW PinPoint-3D 31016) and one solid-state detector (PTW 60017 unshielded Diode E) regarding their suitability for relative dosimetry of the small animal radiation research platform SARRP (220 kVp). The measurements were performed in a high-resolution 3D scanning phantom, centering the detectors in the field following the in-plane and cross-plane profiles method at two depths. Depth dose curves (PDDs) and profiles were measured in water for field sizes ranging from 40 × 40 mm2 to 5 × 5 mm2. Quantitative analysis was performed through global and local dose differences (DDs) between the PDDs and the Advanced Markus parallel plate IC data and through the gamma index (γ) criteria for profiles compared against data from EBT3 films provided by the manufacturer. Compared to the Advanced Markus IC, the PDD results suggest that PinPoint-3D is suitable for depth measurements at this beam quality, even near the surface, with agreements better than 1%. Semiflex 31010 was accurate to within 1.5% for measurements deeper than 5 mm. Diode E showed a dramatic DD and should not be recommended for the field sizes and kVp evaluated in this study. In agreement with γ analyses, PinPoint-3D and Diode E are good candidates for profile measurements of field sizes from 40 × 40 mm2 to 10 × 10 mm2. For 5 × 5 mm2 profiles, only Diode E showed good results, making it a recommended detector for profile measurements.

Feasibility study of the Fricke chemical dosimeter as an independent dosimetric system for the small animal radiation research platform (SARRP).

For the small animal radiation research platform (SARRP) with X-ray beams in the medium energy range (tube operating voltage at 220 kVp), reference dosimetry is based on the AAPM TG-61 recommendations following the in-phantom method. The objective of this study was to evaluate the feasibility of the Fricke solution as a dosimeter to determine the absorbed dose to water. Feasibility studies at this X-ray energy range are not widely available. We evaluated the accuracy, dose linearity and dose rate dependence in a comparison with an NE 2571 Farmer ionization chamber (IC) and measurements in water. The G(Fe3+) factor was calculated from the curve fitting of the chemical yields for two radioactive sources (192Ir and 60Co) and one X-ray system with a tube operating at 150 and 250 kVp. The same methodology was followed for the dependence of the G(Fe3+) value on the energy and the dose agreement assessment for 180 and 200 kVp in the SARRP. The Fricke system exhibits a good linear response over the range of 5-70 Gy and an accuracy better than 2% for a 2 Gy/min dose rate. The dose rate dependence is smaller than 1% for dose rates greater than 1 Gy/min. The dependence of the G(Fe3+) value on the energy is smaller than 0.41%, with dose agreements better than 2%. The feasibility of the dosimeter for measurements at high doses and high dose rates makes it a suitable tool for dosimetric verifications in several preclinical irradiation configurations.

Effects of lanthanum on human lymphocytes viability and DNA strand break.

Lanthanum (La) is a rare-earth metal with applications in agriculture, industry, and medicine. Since lanthanides show a broad spectrum of applications there is an increased risk of contamination for humans. We examined the effects of lanthanum in Jurkat cells and human peripheral lymphocytes (HPL), and we found that it was cytotoxic and genotoxic on both cell lines. Additionally, HPL were more sensitive to La treatment than Jurkat cells and necrosis was the pathway by which La induced cytotoxicity. Vitamin E was able to diminish the DNA strand breaks induced suggesting that oxidative stress may be involved in the genotoxic process.

Anti-MUC1 Aptamer as Carrier Tool of the Potential Radiosensitizer 1,10 Phenanthroline in MCF-7 Breast Cancer Cells.

BACKGROUND: Proteins overexpressed in malignant tissues form important targets in the development of targeted therapeutics, and aptamers comprise an important affinity agent for therapy and drug delivery. In this study, aberrantly expressed mucin 1 glycoprotein was investigated as a therapeutic target in a breast cancer model. MATERIALS AND METHODS: In order to determine the feasibility of using an aptamer against mucin 1 (aptA) as carrier of the cytotoxic compound 1,10-phenanthroline to MCF-7 cells, as a potential radiosensitizer, was studied in experiments using circular dichroism and rhodamine labelling by fluorescent microscopy and flow cytometry. RESULTS: 1,10-Phenanthroline can be intercalated within aptA when complexed with Fe(II) ions, with dissociation constant (Kd) of 30 µM. The complex was subsequently capable of binding to and being internalised in MCF-7 breast cancer cells. CONCLUSION: aptA can carry 1,10-phenanthroline to cancer cells specifically and this complex represents a potential target-directed anticancer therapy.

Aptamers as Delivery Agents of siRNA and Chimeric Formulations for the Treatment of Cancer.

Both aptamers and siRNA technologies have now reached maturity, and both have been validated with a product in the market. However, although pegaptanib reached the market some time ago, there has been a slow process for new aptamers to follow. Today, some 40 aptamers are in the market, but many in combination with siRNAs, in the form of specific delivery agents. This combination offers the potential to explore the high affinity and specificity of aptamers, the silencing power of siRNA, and, at times, the cytotoxicity of chemotherapy molecules in powerful combinations that promise to delivery new and potent therapies. In this review, we report new developments in the field, following up from our previous work, more specifically on the use of aptamers as delivery agents of siRNA in nanoparticle formulations, alone or in combination with chemotherapy, for the treatment of cancer.

210Po concentration in Perna perna mussels: looking for radiation effects.

Twenty ropes with 400 Perna perna mussels seeds (3 cm shell size) were set-up on floating structures at Cabo Frio Island, Arraial do Cabo, approximately 100 km northeast of Rio de Janeiro city. A rope was taken out on a monthly basis, and the shell sizes of 100 seeds were measured. The haemolymph of 10 male and 10 female individuals was taken, and the same individuals were separated for 210Po/210Pb determination. After one year of monthly sampling, no clear correlation was observed between the 210Po concentration, mussel's age and weight. A mean 210Po concentration of 155 Bq kg(-1) wet weight basis, was obtained, which is comparable with data reported in the literature. The radiation dose did not have any observable effect on the micronuclei frequency and DNA breaks in the mussels. This was probably due to the low dose rate, 0.02 mGy d(-1), in comparison with the suggested potential dose limit of 10 mGy d(-1).

Validating Fricke dosimetry for the measurement of absorbed dose to water for HDR 192Ir brachytherapy: a comparison between primary standards of the LCR, Brazil, and the NRC, Canada.

Two Fricke-based absorbed dose to water standards for HDR Ir-192 dosimetry, developed independently by the LCR in Brazil and the NRC in Canada have been compared. The agreement in the determination of the dose rate from a HDR Ir-192 source at 1 cm in a water phantom was found to be within the k = 1 combined measurement uncertainties of the two standards: D NRC/D LCR = 1.011, standard uncertainty = 2.2%. The dose-based standards also agreed within the uncertainties with the manufacturer's stated dose rate value, which is traceable to a national standard of air kerma. A number of possible influence quantities were investigated, including the specific method for producing the ferrous-sulphate Fricke solution, the geometry of the holder, and the Monte Carlo code used to determine correction factors. The comparison highlighted the lack of data on the determination of G(Fe3+) in this energy range and the possibilities for further development of the holders used to contain the Fricke solution. The comparison also confirmed the suitability of Fricke dosimetry for Ir-192 primary standard dose rate determinations at therapy dose levels.

Changes in protein expression due to deleterious mutations in the FA/BRCA pathway.

Inherited deleterious mutations in one of the Fanconi anemia genes lead to a disease, characterized by bone marrow failure, myeloid leukemia, and hypersensitivity to DNA damage. We identified proteins likely associated to the molecular signaling pathways involved in DNA repair of interstrand cross-link lesions and in mechanisms of genomic stability mediated by FA/BRCA pathways. We compared protein maps resolved by bidimensional electrophoresis and analyzed differentially expressed proteins, by mass spectrometry, between FA complementation group C (FANCC)-deficient cells, and their ectopically corrected counterpart in physiological conditions or after treatment with MMC. We found six differentially expressed proteins; among them, the checkpoint mediator protein MDC1 whose expression was disrupted in FANCC-/- cells. The potential role of differentially expressed proteins in FA phenotype is discussed.

Relative output factor and beam profile measurements of small radiation fields with an L-alanine/K-band EPR minidosimeter.

The performance of an L-alanine dosimeter with millimeter dimensions was evaluated for dosimetry in small radiation fields. Relative output factor (ROF) measurements were made for 0.5 x 0.5, 1 x 1, 3 x 3, 5 x 5, 10 x 10 cm(2) square fields and for 5-, 10-, 20-, 40-mm-diam circular fields. In beam profile (BP) measurements, only 1 x 1, 3 x 3, 5 x 5 cm2 square fields and 10-, 20-, 40-mm-diam circular fields were used. For square and circular field irradiations, Varian/Clinac 2100, and a Siemens/Mevatron 6 MV linear accelerators were used, respectively. For a batch of 800 L-alanine minidosimeters (miniALAs) the average mass was 4.3+/-0.5 (1 sigma) mg, the diameter was 1.22+/-0.07 (1 sigma) mm, and the length was 3.5+/-0.2 (l sigma) mm. A K-Band (24 GHz) electron paramagnetic resonance (EPR) spectrometer was used for recording the spectrum of irradiated and nonirradiated miniALAs. To evaluate the performance of the miniALAs, their ROF and BP results were compared with those of other types of detectors, such as an ionization chamber (PTW 0.125 cc), a miniTLD (LiF: Mg,Cu,P), and Kodak/X-Omat V radiographic film. Compared to other dosimeters, the ROF results for miniALA show differences of up to 3% for the smallest fields and 7% for the largest ones. These differences were within the miniALA experimental uncertainty (-5-6% at 1 sigma). For BP measurements, the maximum penumbra width difference observed between miniALA and film (10%-90% width) was less than 1 mm for square fields and within 1-2 mm for circular fields. These penumbra width results indicate that the spatial resolution of the miniALA is comparable to that of radiographic film and its dimensions are adequate for the field sizes used in this experiment. The K-Band EPR spectrometer provided adequate sensitivity for assessment of miniALAs with doses of the order of tens of Grays, making this dosimetry system (K-Band/miniALA) a potential candidate for use in radiosurgery dosimetry.

[Schistosomiasis mansoni in the seminal vesicle]. / Esquistossomose mansônica em vesícula seminal.

In endemic regions, Mansoni schistosomiasis is responsible for high morbidity-mortality rates due to diseases associated with infestation of the hepatic system. Genital involvement caused by Mansoni schistosomiasis is rare. We report the first case of Mansoni schistosomiasis in the seminal vesicle, which was diagnosed incidentally by means of histopathological study of the prostate and seminal vesicles after surgical removal.

Analysis of surgical results and of residual postoperative deformities in preaxial polydactyly of the hand.

PURPOSE: Polydactyly is the most common congenital anomaly of the hand. It may occur as a separate event or as part of a syndrome, with preaxial polydactyly of the hand (or thumb duplication) being the most common among Caucasians. The present study analyzed the surgical results and the residual postoperative deformities of patients with thumb duplication. METHODS: Thirty-one patients with duplicated thumbs were surgically treated from January 2002 to April 2008 and 19 of them, who had returned during the late postoperative period, were evaluated. Each case was typed according to Wassel's classification into seven types and the most common category was type IV. Removal of radial component was done in 18 patients aged on average 51 months. RESULTS: Patients and parents were satisfied with both the functional results and the appearance of the reconstructed thumb. In the subjective evaluation of residual deformities, axis deviation and residual prominence were commonly found. There were coherencies in data between both subjective and objective outcomes. The children that had difficulty in holding very small objects in the subjective functional result were the same children with residual deformities in the objective result. Patient's age at surgery and Wassel's type influenced the analysis of residual postoperative deformities. There was statistically significant difference in cases of type VII and in patients operated at more than three years of age. Correlation between type VII and patient's age at time of surgery was found. The children with type VII duplication were operated later. CONCLUSIONS: For a better result, surgical correction should be performed before three years of age, thus correcting all the changes detected, mainly in type VII, in order to reduce the incidence of residual deformity. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Radiotherapy-Induced Skin Reactions Induce Fibrosis Mediated by TGF-ß1 Cytokine.

PURPOSE: This study aimed to investigate radiation-induced lesions on the skin in an experimental animal model. Methods and Materials: Cutaneous wounds were induced in Wistar rats by 4 MeV energy electron beam irradiation, using a dose rate of 240 cGy/min, for 3 different doses (10 Gy, 40 Gy, and 60 Gy). The skin was observed 5, 10, and 25 days (D) after ionizing radiation exposition. RESULTS: Infiltrate inflammatory process was observed in D5 and D10, for the 40 Gy and 60 Gy groups, and a progressive increase of transforming growth factor ß1 is associated with this process. It could also be noted a mischaracterization of collagen fibers at the high-dose groups. CONCLUSION: It was observed that the lesions caused by ionizing radiation in rats were very similar to radiodermatitis in patients under radiotherapy treatment. ADVANCES IN KNOWLEDGE: This study is important to develop strategies to prevent radiation-induced skin reactions.

Technological aspects of lactose-hydrolyzed milk powder.

Few reports describe the effect of lactose hydrolysis on the properties of milk powder during production and storage. Hence, the aim of this study was to evaluate the effects of five different levels of enzymatic lactose hydrolysis during the production and storage of milk powder. As the lactose hydrolysis rate increased, adhesion to the drying chamber also increased, due to higher levels of particle agglomeration. Additionally, more brown powder was obtained when the lactose hydrolysis rate was increased, which in turn negatively affected rehydration ability. Using Raman spectroscopy, crystallization of the lactose residues in various samples was assessed over 6weeks of accelerated aging at a room temperature environment with 75.5% of air moisture. Products with 25% or greater lactose hydrolysis showed no signs of crystallization, in contrast to the non-hydrolyzed sample.