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Hirschsprung's disease (HSCR) is characterized by congenital absence of ganglion cells in the gastrointestinal tract, which leads to impaired defecation, constipation and intestinal obstruction. The current diagnosis of HSCR is based on Rectal Suction Biopsies (RSBs), which could be complex in newborns. Occasionally, there is a delay in diagnosis that can increase the risk of clinical complications. Consequently, there is room for new non-invasive diagnostic methods that are objective, more logistically feasible and also deliver a far earlier base for a potential surgical intervention. In recent years, microRNA (miRNA) has come into the focus as a relevant early marker that could provide more insights into the etiology and progression of diseases. Therefore, in the search of a non-invasive HSCR biomarker, we analyzed miRNA expression in urine samples of HSCR patients. Results from 5 HSCR patients using microarrays, revealed hsa-miR-378 h, hsa-miR-210-5p, hsa-miR-6876-3p, hsa-miR-634 and hsa-miR-6883-3p as the most upregulated miRNAs; while hsa-miR-4443, hsa-miR-22-3p, hsa-miR-4732-5p, hsa-miR-3187-5p, and hsa-miR-371b-5p where the most downregulated miRNAs. Further search in miRNAwalk and miRDB databases showed that certainly most of these dysregulated miRNAs identified target HSCR associated genes, such as RET, GDNF, BDNF, EDN3, EDNRB, ERBB, NRG1, SOX10; and other genes implied in neuronal migration and neurogenesis. Finally, we could also validate some of these miRNA changes in HSCR urine by RT-qPCR. Altogether, our analyzed HSCR cohort presents a dysregulated miRNA expression presents that can be detected in urine. Our findings open the possibility of using specific urine miRNA signatures as non-invasive HSCR diagnosis method in the future. [ABSTRACT FROM AUTHOR]

Western disturbances (WDs) are synoptic-scale weather systems embedded within the subtropical westerly jet. Manifesting as upper-level troughs often associated with a lower-tropospheric low over western or northern India, they share some dynamical features with extratropical cyclones. WDs are most common during the boreal winter (December to March), during which they bring the majority of precipitation – both rain and snow – to the western Himalaya, as well as to surrounding areas of north India, Pakistan, and the Tibetan Plateau. WDs are also associated with weather hazards such as heavy snowfall, hailstorms, fog, cloudbursts, avalanches, frost, and cold waves. In this paper, we review recent developments in understanding WDs and their impacts. Over the last decade, recent studies have collectively made use of novel data, novel analysis techniques such as tracking algorithms, and the increasing availability of high-resolution weather and climate models. This review is separated into six main sections – structure and thermodynamics, precipitation and impacts, teleconnections, modelling experiments, forecasting at a range of scales, and paleoclimate and climate change – each motivated with a brief discussion of the accomplishments and limitations of previous research. A number of step changes in understanding are synthesised. Use of new modelling frameworks and tracking algorithms has significantly improved knowledge of WD structure and variability, and a more frequentist approach can now be taken. Improved observation systems have helped quantification of water security over the western Himalaya. Convection-permitting models have improved our understanding of how WDs interact with the Himalaya to trigger natural hazards. Improvements in paleoclimate and future climate modelling experiments have helped to explain how WDs and their impacts over the Himalaya respond to large-scale natural and anthropogenic forcings. We end by summarising unresolved questions and outlining key future WD research topics. [ABSTRACT FROM AUTHOR]

Background: The primary objective of this study was to ascertain the risk factors associated with hardware complications following segmental mandibular reconstruction in head and neck cancer patients. Additionally, we sought to develop a nomogram model that enables accurate risk prediction., Methods: Patients who underwent segmental mandibulectomy with immediate free or local regional tissue transfer between January 2016 and December 2020 were reviewed. Hardware complications were defined. Patient demographics and perioperative parameters were analyzed., Results: A total of 510 patients were analyzed. Postoperative radiation therapy (OR = 2.296, 95% CI = 1.339-3.938, p = 0.003), postoperative wound infection (OR = 2.367, 95% CI = 1.472-3.806, p < 0.001), and debridement for flap-related complications (OR = 5.484, 95% CI = 3.269-9.199, p < 0.001) were identified as independent risk factors. The nomogram model demonstrated good discriminatory ability., Conclusion: This comprehensive analysis identified three independent risk factors, and the nomogram provides a valuable tool for predicting the risks. Further research is needed to validate these findings and explore preventive strategies., (© 2024 Wiley Periodicals LLC.)

Objective: The optimal method for maintaining intraoperative blood pressure during microsurgical procedures remains controversial. While intravenous fluid administration is essential, overfilling can lead to complications. Vasopressor agents are used cautiously due to their vasoconstrictive effects, which could potentially lead to flap failure. Numerous studies have explored the possible link between amine administration and free flap failure, yielding inconsistent results. This study aims to determine whether intraoperative norepinephrine administration increases the flap failure rate in microsurgical breast reconstructions., Methods: All women (n = 335) who underwent breast reconstruction using DIEP or PAP flaps (n = 400) in 2018 and 2022 in the Plastic Surgery Department of Georges-Pompidou European Hospital (Paris, France) were included in the study. These patients were classified into two groups based on the intraoperative administration of norepinephrine: the N+ group (50 patients) and the N- group (285 patients). Norepinephrine was administered when systolic blood pressure fell below 90 mmHg or mean arterial pressure (MAP) dropped below 65 mmHg, following fluid resuscitation in 2018, or without prior fluid loading in 2022. The primary endpoint was total flap loss. Secondary endpoints included arterial and venous thrombosis and the need for revision surgeries., Results: Norepinephrine administration significantly increased the risk of total flap loss in DIEP and PAP flap surgeries (p < 0.001). It also heightened the risk of arterial thrombosis (p = 0.002) and venous thrombosis (p = 0.04), and led to a greater number of revision surgeries (p < 0.001). Subgroup analysis indicated that PAP flaps are more sensitive to norepinephrine compared to DIEP flaps., Conclusions: Our study suggests that the intraoperative administration of any dose of norepinephrine is associated with an increased risk of flap failure in breast reconstructive microsurgery using DIEP and PAP flaps., (© 2025 Wiley Periodicals LLC.)