In children with tracheobronchomalacia, surgical management should be reserved for the most severe cases and be specific to the type and location of tracheobronchomalacia. The goal of this study is ...to describe the presentation and outcomes of children with severe tracheobronchomalacia undergoing surgery.
Retrospective case series of 20 children operated for severe tracheobronchomalacia at a tertiary hospital from 2003 to 2023. Data were collected on symptoms age at diagnosis, associated comorbidities, previous surgery, age at surgery, operative approach, time of follow-up, and outcome. Surgical success was defined as symptom improvement.
The most frequent symptoms of severe tracheobronchomalacia were stridor (50 %), cyanosis (50 %), and recurrent respiratory infections (45 %). All patients had one or more underlying conditions, most commonly esophageal atresia (40 %) and prematurity (35 %). Bronchoscopy were performed in all patients. Based on etiology, patients underwent the following procedures: anterior aortopexy (n = 15/75 %), posterior tracheopexy (n = 4/20 %), and/or posterior descending aortopexy (n = 4/20 %). Three patients underwent anterior aortopexy and posterior tracheopexy procedures. After a median follow-up of 12 months, 16 patients (80 %) had improvement in respiratory symptoms. Decannulation was achieved in three (37.5 %) out of eight patients with previous tracheotomy. The presence of dying spells at diagnosis was associated with surgical failure.
Isolated or combined surgical procedures improved respiratory symptoms in 80 % of children with severe tracheobronchomalacia. The choice of procedure should be individualized and guided by etiology: anterior aortopexy for anterior compression, posterior tracheopexy for membranous intrusion, and posterior descending aortopexy for left bronchus obstruction.
Breast cancer (BC) is the most common type of cancer in premenopausal women with germline TP53 pathogenic variants (mTP53) (Li Fraumeni syndrome - LFS). However, little is known about the BC ...prognosis in these patients. This study analyzed the BC-related oncologic outcomes of patients with LFS.
We evaluated a cohort of LFS patients with BC in comparison with a control cohort of BC patients with no pathogenic variant in a hereditary cancer panel. The primary endpoint was recurrence-free survival (RFS). Due to the risk of second malignancies in LFS, only locoregional and distant recurrences were considered events for RFS. Secondary endpoints included rates of contralateral BC, overall survival (OS), and breast cancer-specific survival (BCSS).
Forty-one patients were evaluated in the mTP53 group and 82 in the control group. Median age at BC diagnosis was 40 and 41 years, respectively. The mTP53 group received less adjuvant radiotherapy than the control group (63.4% vs 93.9%, P < 0.001). Other relevant baseline characteristics and treatment received were similar between groups. 5y-RFS rates were 79.4% in the mTP53 versus 93.6% in the control group (HR 2.43, 95%CI 0.74–8.01, P = 0.143); and were not impacted by the use of adjuvant radiotherapy. 5y-BCSS rates were 92.2% and 98.6%, respectively (HR 1.87, IC95% 0.25–13.48, P = 0.534).
Our results showed no statistically significant difference in BC-related RFS and BCSS between patients with mTP53 and a control group with no pathogenic variant. Larger multicentric studies are warranted to confirm these results.
•Women with Li Fraumeni syndrome (LFS) have a high risk of breast cancer (BC).•BC in LFS is frequently estrogen receptor-positive and HER2-positive.•Nevertheless, little is known about BC behavior and prognosis in these patients.•We evaluated BC-related outcomes in LFS, including recurrence-free survival (RFS).•5-year RFS was 79% in the LFS group and 93% in a matched control group (P = 0.143).
Internet of Things (IoT) technologies can greatly benefit from machine-learning techniques and artificial neural networks for data mining and vice versa. In the agricultural field, this convergence ...could result in the development of smart farming systems suitable for use as decision support systems by peasant farmers. This work presents the design of a smart farming system for crop production, which is based on low-cost IoT sensors and popular data storage services and data analytics services on the cloud. Moreover, a new data-mining method exploiting climate data along with crop-production data is proposed for the prediction of production volume from heterogeneous data sources. This method was initially validated using traditional machine-learning techniques and open historical data of the northeast region of the state of Puebla, Mexico, which were collected from data sources from the National Water Commission and the Agri-food Information Service of the Mexican Government.
During mycobacterial infection, macroautophagy/autophagy, a process modulated by cytokines, is essential for mounting successful host responses. Autophagy collaborates with human immune responses ...against Mycobacterium tuberculosis (Mt) in association with specific IFNG secreted against the pathogen. However, IFNG alone is not sufficient to the complete bacterial eradication, and other cytokines might be required. Actually, induction of Th1 and Th17 immune responses are required for protection against Mt. Accordingly, we showed that IL17A and IFNG expression in lymphocytes from tuberculosis patients correlates with disease severity. Here we investigate the role of IFNG and IL17A during autophagy in monocytes infected with Mt H37Rv or the mutant MtΔRD1. Patients with active disease were classified as high responder (HR) or low responder (LR) according to their T cell responses against Mt. IL17A augmented autophagy in infected monocytes from HR patients through a mechanism that activated MAPK1/ERK2-MAPK3/ERK1 but, during infection of monocytes from LR patients, IL17A had no effect on the autophagic response. In contrast, addition of IFNG to infected monocytes, increased autophagy by activating MAPK14/p38 α both in HR and LR patients. Interestingly, proteins codified in the RD1 region did not interfere with IFNG and IL17A autophagy induction. Therefore, in severe tuberculosis patients' monocytes, IL17A was unable to augment autophagy because of a defect in the MAPK1/3 signaling pathway. In contrast, both IFNG and IL17A increased autophagy levels in patients with strong immunity to Mt, promoting mycobacterial killing. Our findings might contribute to recognize new targets for the development of novel therapeutic tools to fight the pathogen.
Mutations in the cellular prion protein associated to familial prion disorders severely increase the likelihood of its misfolding into pathogenic conformers. Despite their postulation as incompatible ...elements with the native fold, these mutations rarely modify the native state structure. However they variably have impact on the thermodynamic stability and metabolism of PrP(C) and on the properties of PrP(Sc) aggregates. To investigate whether the pathogenic mutations affect the dynamic properties of the HuPrP(125-229) α-fold and find possible common patterns of effects that could help in prophylaxis we performed a dynamic diagnosis of ten point substitutions.
Using all-atom molecular dynamics simulations and novel analytical tools we have explored the effect of D178N, V180I, T183A, T188K, E196K, F198S, E200K, R208H, V210I and E211Q mutations on the dynamics of HuPrP(125-228) α-fold. We have found that while preserving the native state, all mutations produce dynamic changes which perturb the coordination of the α2-α3 hairpin to the rest of the molecule and cause the reorganization of the patches for intermolecular recognition, as the disappearance of those for conversion inhibitors and the emergence of an interaction site at the β2-α2 loop region.
Our results suggest that pathogenic mutations share a common pattern of dynamical alterations that converge to the conversion of the β2-α2 loop into an interacting region that can be used as target for interference treatments in genetic diseases.
Homologous recombination is initiated by nucleolytic degradation (resection) of DNA double-strand breaks (DSBs). DSB resection is a two-step process in which an initial short-range step is catalyzed ...by the Mre11-Rad50-Xrs2 (MRX) complex and limited to the vicinity of the DSB end. Then the two long-range resection Exo1 and Dna2-Sgs1 nucleases extend the resected DNA tracts. How short-range resection is regulated and contributes to checkpoint activation remains to be determined. Here, we show that abrogation of long-range resection induces a checkpoint response that decreases DNA damage resistance. This checkpoint depends on the 9-1-1 complex, which recruits Dpb11 and Rad9 at damaged DNA. Furthermore, the 9-1-1 complex, independently of Dpb11 and Rad9, restricts short-range resection by negatively regulating Mre11 nuclease. We propose that 9-1-1, which is loaded at the leading edge of resection, plays a key function in regulating Mre11 nuclease and checkpoint activation once DSB resection is initiated.
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•The 9-1-1 complex induces a checkpoint in the absence of both Exo1 and Sgs1•Checkpoint activation decreases DNA damage resistance of exo1Δ sgs1Δ cells•The 9-1-1 complex negatively regulates short-range resection•The 9-1-1 complex restricts Mre11 nuclease close to the double-strand break end
Resection of DNA double-strand breaks is a two-step process that relies on short and long-range nucleases. Gobbini et al. show that the 9-1-1 complex plays a dual function during short-range resection, promoting checkpoint activation by recruiting Rad9 at damaged sites and negatively regulating short-range resection in a Rad9-independent manner by restricting Mre11 nuclease.
Determining how the galactic environment, especially the high gas densities and complex dynamics in bar-fed galaxy centers, alters the star formation efficiency (SFE) of molecular gas is critical to ...understanding galaxy evolution. However, these same physical or dynamical effects also alter the emissivity properties of CO, leading to variations in the CO-to-H2 conversion factor (αCO) that impact the assessment of the gas column densities and thus of the SFE. To address such issues, we investigate the dependence of αCO on the local CO velocity dispersion at 150 pc scales using a new set of dust-based αCO measurements and propose a new αCO prescription that accounts for CO emissivity variations across galaxies. Based on this prescription, we estimate the SFE in a sample of 65 galaxies from the PHANGS–Atacama Large Millimeter/submillimeter Array survey. We find increasing SFE toward high-surface-density regions like galaxy centers, while using a constant or metallicity-based αCO results in a more homogeneous SFE throughout the centers and disks. Our prescription further reveals a mean molecular gas depletion time of 700 Myr in the centers of barred galaxies, which is overall three to four times shorter than in nonbarred galaxy centers or the disks. Across the galaxy disks, the depletion time is consistently around 2–3 Gyr, regardless of the choice of αCO prescription. All together, our results suggest that the high level of star formation activity in barred centers is not simply due to an increased amount of molecular gas, but also to an enhanced SFE compared to nonbarred centers or disk regions.
To describe the symptoms and clinical course of SARS-CoV-2 infection in patients with cystic fibrosis (CF).
We carried out a prospective multicentre cohort study based on 32 CF centres and 6597 ...patients. Centres were contacted to collect baseline and follow-up data of patients who reported symptoms suggestive of COVID-19 or who had contact with a positive/suspected case between the end of February and July 2020. Symptoms and clinical course of the infection were compared between patients who tested positive by molecular testing (cases) and those who tested negative (controls).
Thirty patients were reported from the centres, 16 of them tested positive and 14 tested negative. No differences in symptoms and outcome of the disease were observed between groups. Fever, cough, asthenia and dyspnea were the most frequently reported symptoms. Eight cases (50%) were hospitalized but none required ICU admission. Two adults with a history of lung transplant required non-invasive ventilation, none required ICU admission and all patients fully recovered without short-term sequelae.
The course of SARS-CoV-2 in our patients was relatively favorable. However, COVID-19 should not be considered a mild disease in CF patients, particularly for those with severely impaired respiratory function and organ transplant.
Purpose
Clinical data on patients with intra-abdominal candidiasis (IAC) is still scarce.
Methods
We collected data from 13 hospitals in Italy, Spain, Brazil, and Greece over a 3-year period ...(2011–2013) including patients from ICU, medical, and surgical wards.
Results
A total of 481 patients were included in the study. Of these, 27 % were hospitalized in ICU. Mean age was 63 years and 57 % of patients were male. IAC mainly consisted of secondary peritonitis (41 %) and abdominal abscesses (30 %); 68 (14 %) cases were also candidemic and 331 (69 %) had concomitant bacterial infections. The most commonly isolated
Candida
species were
C. albicans
(
n
= 308 isolates, 64 %) and
C. glabrata
(
n
= 76, 16 %). Antifungal treatment included echinocandins (64 %), azoles (32 %), and amphotericin B (4 %). Septic shock was documented in 40.5 % of patients. Overall 30-day hospital mortality was 27 % with 38.9 % mortality in ICU. Multivariate logistic regression showed that age (OR 1.05, 95 % CI 1.03–1.07,
P
< 0.001), increments in 1-point APACHE II scores (OR 1.05, 95 % CI 1.01–1.08,
P
= 0.028), secondary peritonitis (OR 1.72, 95 % CI 1.02–2.89,
P
= 0.019), septic shock (OR 3.29, 95 % CI 1.88–5.86,
P
< 0.001), and absence of adequate abdominal source control (OR 3.35, 95 % CI 2.01–5.63,
P
< 0.001) were associated with mortality. In patients with septic shock, absence of source control correlated with mortality rates above 60 % irrespective of administration of an adequate antifungal therapy.
Conclusions
Low percentages of concomitant candidemia and high mortality rates are documented in IAC. In patients presenting with septic shock, source control is fundamental.
Population data on tobacco use and its determinants require continuous monitoring and careful inter-country comparison. We aimed to provide the most up-to-date estimates on tobacco smoking from a ...large cross-sectional survey, conducted in selected European countries.
Within the TackSHS Project, a face-to-face survey on smoking was conducted in 2017-2018 in 12 countries: Bulgaria, England, France, Germany, Greece, Ireland, Italy, Latvia, Poland, Portugal, Romania, and Spain, representing around 80% of the 432 million European Union (EU) adult population. In each country, a representative sample of around 1,000 subjects aged 15 years and older was interviewed, for a total of 11,902 participants.
Overall, 25.9% of participants were current smokers (31.0% of men and 21.2% of women, P < 0.001), while 16.5% were former smokers. Smoking prevalence ranged from 18.9% in Italy to 37.0% in Bulgaria. It decreased with increasing age (compared to <45, multivariable odds ratio OR for ≥65 year, 0.31; 95% confidence interval CI, 0.27-0.36), level of education (OR for low vs high, 1.32; 95% CI, 1.17-1.48) and self-rated household economic level (OR for low vs high, 2.05; 95% CI, 1.74-2.42). The same patterns were found in both sexes.
These smoking prevalence estimates represent the most up-to-date evidence in Europe. From them, it can be derived that there are more than 112 million current smokers in the EU-28. Lower socio-economic status is a major determinant of smoking habit in both sexes.
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