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AIMS: The aims of this article are to provide an overview of the technique of phalloplasty by radial forearm free flap in the context of female-to-male gender reassignment surgery, with a specific focus on surgical technical details and the prevention of postoperative complications. METHODS: In the light of our 30 years of experience in caring for female-to-male transgender individuals and conducting a critical review of the literature, we exhaustively present our technique of radial forearm free flap phalloplasty in female-to-male gender reassignment surgery. RESULTS: The technique of radial forearm free flap phalloplasty, utilizing a one-stage approach for neourethral and neophallus construction based on the "tube within a tube" principle, not only achieves an aesthetically pleasing appearance of the neophallus resembling a normal penis with tactile and erogenous sensitivities but also yields a functional neourethra and satisfactory penile rigidity using implants for standing voiding and sexual intercourse. This intricate surgical procedure demands not only meticulous execution of all surgical maneuvers but also high-level postoperative care. Despite refinements in technique over recent decades, aesthetic sequelae at the donor site of the flap remain subject to criticism, and postoperative complications, particularly of vascular and urological nature, remain significant. CONCLUSION: Future optimization of the surgical technique for this procedure will be imperative to minimize postoperative complications and establish a true technical "gold standard" for phalloplasty in female-to-male transgender individuals.

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BACKGROUND: Mismatch repair-deficient (dMMR) tumors displaying microsatellite instability (MSI) represent a paradigm for the success of immune checkpoint inhibitor (ICI)-based immunotherapy, particularly in patients with metastatic colorectal cancer (mCRC). However, a proportion of patients with dMMR/MSI mCRC exhibit resistance to ICI. Identification of tools predicting MSI mCRC patient response to ICI is required for the design of future strategies further improving this therapy. PATIENTS AND METHODS: We combined high-throughput DNA and RNA sequencing of tumors from 116 patients with MSI mCRC treated with anti-programmed cell death protein 1 ± anti-cytotoxic T-lymphocyte-associated protein 4 of the NIPICOL phase II trial (C1, NCT03350126, discovery set) and the ImmunoMSI prospective cohort (C2, validation set). The DNA/RNA predictors whose status was significantly associated with ICI status of response in C1 were subsequently validated in C2. Primary endpoint was progression-free survival by immune RECIST (iRECIST) (iPFS). RESULTS: Analyses showed no impact of previously suggested DNA/RNA indicators of resistance to ICI, e.g. MSIsensor score, tumor mutational burden, or specific cellular and molecular tumoral contingents. By contrast, iPFS under ICI was shown in C1 and C2 to depend both on a multiplex MSI signature involving the mutations of 19 microsatellites hazard ratio cohort C2 (HRC2) = 3.63; 95% confidence interval (CI) 1.65-7.99; P = 1.4 × 10-3] and the expression of a set of 182 RNA markers with a non-epithelial transforming growth factor beta (TGFB)-related desmoplastic orientation (HRC2 = 1.75; 95% CI 1.03-2.98; P = 0.035). Both DNA and RNA signatures were independently predictive of iPFS. CONCLUSIONS: iPFS in patients with MSI mCRC can be predicted by simply analyzing the mutational status of DNA microsatellite-containing genes in epithelial tumor cells together with non-epithelial TGFB-related desmoplastic RNA markers.

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Inherited metabolic diseases (IMD) form a heterogeneous group of genetic disorders that surface primarily during childhood and result in significant morbidity and mortality. A prevalence of 1 in 2500-5000 live births is often reported. The transfer of adolescents from pediatric care to adult health facilities is often difficult for patients and their families and can lead to a breakdown in medical follow-up and therefore serious complications. Existing recommendations for the successful transition of patients with chronic disorders do not specifically address patients with IMDs associated with dietary treatment. Here, the French network for rare inherited metabolic diseases (G2M) presents its reflections and recommendations for a successful transition. Preparations for the transfer must be made well in advance. The transfer must aim for adolescents gaining autonomy by making them responsible and providing them with the knowledge that will enable them to manage their care themselves, know how to react appropriately if there is any change in their condition, and move comfortably within the adult healthcare system. This requires the active participation of the patient, his or her family, and pediatric and adult care teams. It involves multidisciplinary management plus the production and maintenance of an educational therapy program. Finally, the identification of physicians and dietitians trained in IMDs, relevant subspecialists, and even expert patients could improve the continuum of complete and appropriate care for these patients within adult medicine.

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The photoswitching and competitive processes of two photochromic dithienylethenes (DTEs) functionalized at both sides with 2-ureido-4[1H]-pyrimidone (UPy) quadruple hydrogen-bonding recognition patterns have been investigated with NMR experiments, ultrafast spectroscopy, and density functional theory (DFT) calculations. The originality of these molecules is their ability to form large supramolecular assemblies induced by light for the closed form (CF) species while the open form (OF) species exist as small oligomers. Photochromic parameters have been determined and photochemical pathways have been rationalized with clear distinction between the antiparallel (OF-AP) and parallel (OF-P) species. A new photocyclization pathway via triplet manifold has been evidenced. The effect of the supramolecular assembly on the photochemical response is discussed. Unlike the photoreversion process, which is unaffected by supramolecular assembly, rate constants of the photocyclization reaction and intersystem crossing process are sensitive to the presence of small OF oligomers.

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INTRODUCTION: Whether clinical prediction rules for pulmonary embolism are accepted and used among general internal medicine residents remains uncertain. We therefore evaluated the frequency of use and acceptability of the Revised Geneva Score (RGS) and the Pulmonary Embolism Severity Index (PESI), and explored which factors were associated with rule use. MATERIALS/METHODS: In an online survey among general internal medicine residents from 10 Swiss hospitals, we assessed rule acceptability using the Ottawa Acceptability of Decision Rules Instrument (OADRI) and explored the association between physician and training-related factors and rule use using mixed logistic regression models. RESULTS: The response rate was 50.4% (433/859). Overall, 61% and 36% of the residents reported that they always or regularly use the RGS and the PESI, respectively. The mean overall OADRI score was 4.3 (scale 0-6) for the RGS and 4.1 for the PESI, indicating a good acceptability. Rule acceptability (odds ratio [OR] 6.19 per point, 95% confidence interval [CI] 3.64-10.51), prior training in emergency medicine (OR 5.14, CI 2.20-12.01), and availability of internal guidelines recommending RGS use (OR 4.25, CI 2.15-8.43) were associated with RGS use. Rule acceptability (OR 6.43 per point, CI 4.17-9.92) and rule taught at medical school (OR 2.06, CI 1.24-3.43) were associated with PESI use. CONCLUSIONS: The RGS was more frequently used than the PESI. Both rules were considered acceptable. Rule acceptability, prior training in emergency medicine, availability of internal guidelines, and rule taught at medical school were associated with rule use and represent potential targets for quality improvement interventions.

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In the current work, accurate quantification over 10 to 108 DNA copies has been successfully achieved for the first time by real-time electrochemical PCR. This has been made possible thanks to the combined use of a fully automated house-built electrochemical qPCR device, optimized for parallel heating and electrochemical monitoring of up to 48 PCR solutions, and the appropriate selection of a DNA intercalating redox probe retaining a strong affinity binding to ds-DNA at the PCR measurement temperature of 72 °C (corresponding to the PCR elongation step). This has also been achieved through the identification of the key parameters governing the onset electrochemical signal decrease and amplitude signal decrease as a function of the PCR cycle for a given DNA intercalating redox probe, thus allowing us to predict the electrochemical PCR kinetic plots from the values of the DNA affinity binding constant determined as a function of temperature. To the best of our knowledge, the analytical performances of the current electrochemical qPCR outperform all of those previously published, in terms of detection limit, dynamic range, reproducibility and melting curve analysis compared to that achieved on a commercialized bench-top fluorescence-based qPCR instrument.

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The current procedure of rapeseed oil extraction is based on a first extraction step by pressing followed by a second extraction step with hexane. This solvent being toxic for the users, the consumers and the environment, its use could be forbidden within the coming years. Stimulated by a stringent regulation, the research activity for the replacement of toxic solvents shows a significant development. The aim of this study was to select alternative solvent to hexane such as ethanol or isopropanol, and, to adjust the oil extraction process by developing an ultrasound assisted method. The objective was to reach a comparable efficiency but also to enhance the oil quality. When applied to isopropanol, the ultrasound assisted extraction method has shown promising results, and comparable to those obtained with hexane (oil yield of 80% for hexane and 79% for isopropanol at optimum extraction conditions (20min of ultrasound pretreatment followed by 2h of additional solid/liquid extraction)). Conversely, in studied conditions, ethanol did not seem to be an appropriate alternative solvent to hexane as the extraction yields obtained by using this solvent were quite low.

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The photoswitching and competitive processes of the referent photochromic diarylethene derivative 1,2-bis(2,4-dimethyl-5-phenyl-3-thienyl)perfluorocyclopentene (DTE) and a novel bridged analog DTE-m5 have been investigated by state-of-the-art TD-DFT calculations and ultrafast spectroscopy supported by advanced chemometric data treatments. Focusing on DTE, the overall deactivation pathway of both antiparallel (AP) and parallel (P) conformers of the open form (OF) (1 : 1 in solution) has been resolved and rationalized starting from the Franck-Condon (FC) region to the ground state recovery. For the photo-excited P conformer, after ultrafast relaxation (∼200 fs) towards the S1 relaxed state, an expected ISC occurred (55 ps) to produce a triplet state, 3P, the latter relaxing within 2.5 µs. Concerning the AP conformer, the photocyclization reaction is reported to proceed immediately (100 fs) starting from the FC region while the relaxed singlet state is populated in parallel. For the first time, we discovered that the latter state evolves through an unexpected ISC process (1 ps) giving rise to a second triplet state,3AP. For DTE-m5, by slightly constraining the molecule with the bridge, this triplet becomes reactive and participates in the formation of 10% of closed form (CF) probably through an adiabatic mechanism. Concerning the photoreversion, in accordance with the literature, we report on a two-step process, a 190 fs vibrational relaxation followed by a 6 ps ring-opening reaction. For the overall species at the singlet or triplet manifold, the use of advanced MCR-ALS allows us to obtain specific spectral signatures. This study is therefore a new step within the comprehension of DTE photochemistry.

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UNLABELLED: Essentials Lower limb ultrasonography (CUS) could be useful in suspected pulmonary embolism (PE). We performed a metaanalysis on the diagnostic characteristics of CUS in suspected PE. With a sensitivity of 41%, proximal CUS would be positive in one of every 7.3 patients. Complete CUS has a higher sensitivity but specificity for PE is too low to use it in suspected PE. SUMMARY: Background Diagnosis of pulmonary embolism (PE) is commonly based on D-dimer measurement and computed tomography (CT) angiography. Lower limb vein compression ultrasonography (CUS) for diagnosing deep vein thrombosis may be of interest in patients with suspected PE. Objectives We aimed to summarize the data on the diagnostic characteristics of CUS in suspected PE patients. Patients/Methods We conducted a literature review by using PUBMED and EMBASE and included 15 prospective studies in which CUS was performed in consecutive patients with suspected PE. Results Of the 6991 included patients, 2001 (30%) had pulmonary embolism. Eight of the 15 studies included only outpatients, two included hospitalized patients and five involved both in- and outpatients. In 13 studies, only proximal CUS was performed. Two studies analyzed the added value of distal CUS including the calf veins (whole-leg CUS). Pooled estimate of proximal CUS sensitivity was 41% (95% confidence interval [CI], 36-46%) with strong heterogeneity (I square, 79%). Specificity of proximal CUS was 96% (95% CI, 94-98%). The overall positive likelihood ratio for proximal CUS was 11.9 (95% CI, 7.1-19.8), whereas the overall negative likelihood ratio was 0.6 (95% CI, 0.5-0.7). The sensitivity of whole-leg CUS was 79% (95% CI, 24-98%) and specificity was 84% (95% CI, 76-90%). Conclusions Proximal CUS has low sensitivity and cannot be used to rule out PE. Nevertheless, its high specificity allows confirming PE, which may be useful in patients with contraindications to CT angiography. Whole-leg CUS has a higher sensitivity but low specificity for PE and can therefore not be recommended.

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Foot pressure ulcers are a common complication of diabetes because of patient's lack of sensitivity due to neuropathy. Deep pressure ulcers appear internally when pressures applied on the foot create high internal strains nearby bony structures. Monitoring tissue strains in persons with diabetes is therefore important for an efficient prevention. We propose to use personalized biomechanical foot models to assess strains within the foot and to determine the risk of ulcer formation. Our workflow generates a foot model adapted to a patient's morphology by deforming an atlas model to conform it to the contours of segmented medical images of the patient's foot. Our biomechanical model is composed of rigid bodies for the bones, joined by ligaments and muscles, and a finite element mesh representing the soft tissues. Using our registration algorithm to conform three datasets, three new patient models were created. After applying a pressure load below these foot models, the Von Mises equivalent strains and "cluster volumes" (i.e. volumes of contiguous elements with strains above a given threshold) were measured within eight functionally meaningful foot regions. The results show the variability of both location and strain values among the three considered patients. This study also confirms that the anatomy of the foot has an influence on the risk of pressure ulcer.

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Using a combination of advanced DFT/TDDFT calculations together with ultrafast and stationary spectroscopies we have investigated the photochemistry and cationic complexation ability of 1-pyridinio-benzimidazolate (PyB) and analogs substituted by 15-aza-5-crown (PyB-Aza) or dimethyl-amino groups (PyB-DiMe). Focusing on PyB-Aza, the first aim was to assess the competitive complexation of the imidazole bridge vs. the macrocycle. In acetonitrile, it was found by absorption and emission that the imidazole moiety binds efficiently through lateral electrostatic interaction of high charge density cations and especially Ca(2+) to form a 1 : 1, metal : ligand (M : L) complex. Modulation of the complexation toward para substitution of the phenyl ring with a donor group is reported with values ranging from log K = 3.4 to 6.8. Complexation values are properly predicted by DFT calculations. From a photochemical point of view, for the same series, the trend is parallel to the rate of the photo-release process, found to be less than 200 femtosecond (fs), the fastest photorelease characteristic time reported so far. Unlike photoinduced charge transfer molecules linked with an aza-crown group, the mechanism appears simpler with no participation of loose complexes due to the macrocavity effect. Relaxation mechanisms after cation ejection are discussed as well. Finally, even if any photoinduced translocation of cation is reported for the PyB-Aza molecule between two complexation sites, a discussion about the use of betaine pyridinium as a molecular tool for the smart manipulation of cation systems is initiated.

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The incidence of atrial fibrillation increases with age as does the risk of subsequent ischemic stroke. Falls are a frequent problem in the geriatric population and often hamper the clinician in prescribing anticoagulants despite an indication based on the CHA2DS2-VASc score for fear of intracranial bleeding. This paper reviews the evidence on the safety of oral anticoagulants in this population. Based on observational data, being at risk for falls does not appear to be an absolute contraindication to oral anticoagulants.

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Heart failure with preserved ejection fraction (HF-PEF) represents half of all heart failure. Morbi-mortality for HF-PEF is similar to that of reduced ejection fraction HF (HF-REF). Diagnosis of HF-REF is difficult because of the lack of highly specific criteria. It is based on the presence of signs and symptoms of heart failure, associated with a preserved or moderately decreased left ventricular function, the absence of left ventricular dilatation, and the presence of relevant structural disease such as left ventricular hypertrophy. Despite the use of prognosis modifying drugs commonly used for HF-REF, no therapeutic strategy has been shown to reduce morbi-mortality of HF-PEF. Evidence based guidelines are limited. Management of HF-PEF therefore resides in treatment of high blood pressure and cardiac rate, that of comorbidities, and the use of diuretics in case of congestion.

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Most posterior heel ulcers are the consequence of inactivity and prolonged time lying down on the back. They appear when pressures applied on the heel create high internal strains and the soft tissues are compressed by the calcaneus. It is therefore important to monitor those strains to prevent heel pressure ulcers. Using a biomechanical lower leg model, we propose to estimate the influence of the patient-specific calcaneus shape on the strains within the foot and to determine if the risk of pressure ulceration is related to the variability of this shape. The biomechanical model is discretized using a 3D Finite Element mesh representing the soft tissues, separated into four domains implementing Neo Hookean materials with different elasticities: skin, fat, Achilles' tendon, and muscles. Bones are modelled as rigid bodies attached to the tissues. Simulations show that the shape of the calcaneus has an influence on the formation of pressure ulcers with a mean variation of the maximum strain over 6.0 percentage points over 18 distinct morphologies. Furthermore, the models confirm the influence of the cushion on which the leg is resting: a softer cushion leading to lower strains, it has less chances of creating a pressure ulcer. The methodology used for patient-specific strain estimation could be used for the prevention of heel ulcer when coupled with a pressure sensor.

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Huntington's disease is currently incurable, but cell therapy is seen as a promising alternative treatment. We analyze the safety and efficacy of the intrastriatal transplantation of human fetal neuroblasts from ganglionic eminences in patients with Huntington's disease. A few rare surgical incidents were reported, but the main difficulty associated with this therapeutic approach is the occurrence of recipient alloimmunization against the graft and the lack of availability, standardization and quality control for the fetus-derived products required for cell therapy. Some patients showed sustained cognitive improvement over periods of more than six years, and motor improvements for more than four years. Grafting outcomes are variable even within individual transplantation centers. The reasons for this variability are poorly understood, highlighting the need for further research in this specific area. With the perspective of additional trials in the future, we review here the development of human pluripotent stem cell-derived cell therapy products for HD, and their advantages and disadvantages with respect to fetal cells.

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