The role of nasal washes in CF patients affected by chronic rhinosinusitis

Cystic Fibrosis (CF) presents multiorgan manifestations that include chronic rhinosinusitis (CRS) with or without nasal polyposis. Nasal washes (NWs) are widely used in clinical practice especially in CF patients, although their effectiveness on Ear Nose Throat (ENT) symptoms is controversial. In this study we evaluate the performance and the safety of a NWs solution, with or without surfactant, to reduce symptoms and bacterial load. Materials and methods We enrolled 20 CF patients (mean age: 27,6 years) with CRS, confirmed by nasal endoscopy. All patients, colonized by Pseudomonas Aeruginosa, performed daily a NW by physiological solution or by saline solution with surfactant (Naridek). All patients, at the time of enrollment, filled out a sinonasal questionnaire (SANQ11) and they received instructions for proper washing. During follow-up, we evaluated the reduction of the bacterial load in the nasal lavage. We assess the nasal cavities by endoscopy (2.7 mm 30° rigid endoscope - Storz, Tuttlingen, Germany) according to a modified Lund Kennedy endoscopic scoring system: - rhinorrhea (present = 0, mild = 1, purulent = 2); - edema, and hyperemia (absent = 0, mild = 1 or severe =2) - nasal mucosa (eutrophic = 1; hyperemic = 2; dystrophic = 3); - left and right turbinate hypertrophy (none = 0; mild = 1; medium = 2; and serious = 3). All subjects underwent the Sniffin’Sticks to evaluate the olfactory performance. Results Twelve patients completed 4 months of treatment: 6 patients performed the treatment with Naridek and 6 patients with physiological solution. Due to the small sample size, the scores were added together to have an overall indication of the treatment. (Table1) Nasal endoscopy ENT signs score Olfactory performance SNAQ 11 Naridek V1 80 72* 169 197** Naridek V4 15* 15* 159 98** Physiological solution V1 68 61 151 166 Physiological solution V4 52 39 159 152 *P<0.05 ** p< 0,01 The bacterial colonization in NWs shows no statistically significant difference. However, in 2 patients, we detected a reduction of the bacterial load. While there was no difference in the saline-treated group. Conclusions Considering our small sample we can only draw some great deal to think about: - treatment with NWs allows an improvement of the ENT symptoms and is well tolerated by patients. These data are confirmed by the ENT signs score and by the reduction of the SNAQ11 score in both treatment arms; - the solution with surfactant (Naridek) significantly improves the ENT signs and decreases the nasal endoscopy and the SNAQ11 scores; - no benefit was detected at the evaluation of olfactory performance. In conclusion, even if further confirmations are necessary on broader cases, it seems to emerge as significant the role of surfactant in the therapeutic advantage of NWs

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P &lt; 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P &lt; 0.001), sNox2-dp (r(s), -0.57; P &lt; 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P &lt; 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Getting the 'most out of the hotspot' for practical conservation of groundwater biodiversity

Conservation planning aimed at halting biodiversity loss has seldom focused on groundwater environments due to the lack of suitable management tools and data. Using harpacticoid crustaceans as a test case, we explore the potential of implementing an approach based on Conservation-Relevant Hotspots for practical conservation of groundwater biodiversity. Conservation-Relevant Hotspots are identified by intersecting species richness, endemicity, and taxonomic distinctness with the aim to minimize the total area to protect. We show that, by targeting five Conservation-Relevant Hotspots that cover only 1.9% of the European land surface, one would protect as much as 44% of the harpacticoid crustacean richness, 93% of its endemicity, and 98% of its taxonomic distinctness. About 28% of the area occupied by these hotspots overlaps with protected areas, which calls for an increase in their protection coverage. Our framework proved a useful tool for conservation planning of environments where spatial or socio-economic constraints occur.Peer reviewe

The role of nasal washes in patients with Cystic Fibrosis affected by chronic rhinosinusitis

Cystic Fibrosis (CF) presents multiorgan manifestations that include chronic rhinosinusitis (CRS) with or without nasal polyposis. Nasal washes (NWs) are widely used in clinical practice especially in CF patients, although their effectiveness on Ear Nose Throat (ENT) symptoms is controversial. In this study we evaluate the performance and the safety of a NWs solution, with or without surfactant, to reduce symptoms and bacterial load. Materials and methods We enrolled 20 CF patients (mean age: 27,6 years) with CRS, confirmed by nasal endoscopy. All patients, colonized by Pseudomonas Aeruginosa, performed daily a NW by physiological solution or by saline solution with surfactant (Naridek). All patients, at the time of enrollment, filled out a sinonasal questionnaire (SANQ11) and they received instructions for proper washing. During followup, we evaluated the reduction of the bacterial load in the nasal lavage. We assessed the nasal cavities by endoscopy (2.7 mm 30° rigid endoscope - Storz, Tuttlingen, Germany) according to a modified Lund Kennedy endoscopic scoring system: - rhinorrhea (present = 0, mild = 1, purulent = 2); - edema, and hyperemia (absent = 0, mild = 1 or severe =2) - nasal mucosa (eutrophic = 1; hyperemic = 2; dystrophic = 3); - left and right turbinate hypertrophy (none = 0; mild = 1; medium = 2; and serious = 3). All subjects underwent the Sniffin’Sticks to evaluate the olfactory performance. Results Twelve patients completed 4 months of treatment: 6 patients performed the treatment with Naridek and 6 patients with physiological solution. Due to the small sample size, the scores were added together to have an overall indication of the treatmen

Role of Biophysical Parameters on ex Vivo and in Vivo Gene Transfer to the Airway Epithelium by Polyethylenimine/Albumin Complexes

Efficient gene transfer to the airways by nonviral vectors is a function of different parameters, among which the size and the charge of the transfecting particles. The aim of this study was to determine the transfection efficiency of polyethylenimine (PEI)/albumin polyplexes in ex vivo and in vivo models of respiratory epithelium and to correlate it with biophysical characteristics of the particles. Complexes were obtained by adding different amounts of human serum albumin (HSA) to PEI polyplexes preformed in saline. The presence of HSA caused the formation of bigger and more negative polyplexes and increased PEI transfection efficiency in primary respiratory epithelial cells by 4-6-fold. For in vivo administration to the lung, PEI polyplexes were formed in water and optimized with respect to the N/ P ratio. PEI/pC-Luc complexes gave the highest luciferase expression at N/ P 15 when administered through the trachea. At this N/ P ratio, the size and the surface charge of albumin-containing polyplexes were not different as compared with plain PEI polyplexes. Formulation of PEI polyplexes in the presence of HSA or murine serum albumin (MSA) resulted in a 2-fold increase in luciferase expression. In mice treated with PEI or PEI/MSA polyplexes containing the nuclear beta-gal gene, X-gal staining revealed that transfected cells localized at the bronchiolar epithelium and that PEI/MSA transfected four times as many cells as PEI ( p < 0.05). Finally, double administration of PEI/MSA polyplexes resulted in a further enhancement of transfection of the lung. Our data show that serum albumin enhances PEI-mediated gene transfer to airway epithelial cells in vivo, likely facilitating the uptake of polyplexes, and indicate that this formulation would fulfill the requirement of repeated administration, as necessary in chronic lung diseases like cystic fibrosis

Metformin versus myoinositol: which is better in obese PCOS patients? A randomized controlled crossover study

CONTEXT: due to the central role of metabolic abnormalities in the pathophysiology of PCOS, insulin sensitising agents have been proposed as a feasible treatment option. OBJECTIVE: to investigate which is the more effective between metformin and myoinositol on hormonal, clinical and metabolic parameters in obese patients with polycystic ovary syndrome (PCOS). STUDY DESIGN: crossover randomized-controlled study. PATIENTS: Thirty-four PCOS obese women (age: 25.62 \ub1 4.7 years; BMI: 32.55 \ub1 5.67 kg/m2 ) were randomized to receive metformin (850 mg twice a day) or myoinositol (1000 mg twice a day) for six months. After a three month washout, the same subjects received the other compound for the following six months. MEASUREMENTS: Ultrasonographic pelvic examinations, hirsutism score, anthropometric and menstrual pattern evaluation, hormonal profile assays, oral glucose tolerance test (OGTT) and lipid profile at baseline and after 6 months of treatment were performed. RESULTS: Both metformin and myoinositol significantly reduced the insulin response to OGTT and improved insulin sensitivity. Metformin significantly decreased body weight, and improved menstrual pattern and Ferriman-Gallwey score. Metformin treatment was also associated with a significant decrease in LH and estradiol levels, androgens and AMH levels. None of these clinical and hormonal changes were observed during myoinositol administration. CONCLUSIONS: Both treatments improved the glyco-insulinaemic features of obese PCOS patients,but only metformin seems to exert a beneficial effect on the endocrine and clinical features of the syndrome. This article is protected by copyright. All rights reserve

Isotopic reconstruction of the subsistence strategy for a Central Italian Bronze Age community (Pastena cave, 2nd millennium BCE)

The Pastena cave is located in central Italy, and its best-preserved sector is Grotticella W2, which is dated radiometrically to the Early-Middle Bronze Age. The aim of this paper is to explore human diet, animal husbandry, and plant management, analysing the findings there discovered. Carbon and nitrogen stable isotope analysis was carried out on 40 charred seeds, six faunal remains, and four human individuals, investigating the whole bio-archaeological material available. To the best of our knowledge, this is one of the first papers presenting stable isotope analysis on carpological remains dated to the Italian Early-Middle Bronze Age. The obtained results are consistent with a diet based on terrestrial protein, mainly on plants, and secondly on animal products. The data suggest that plants, especially broad beans, were partially subjected to human management, while livestock was managed through different husbandry strategies. The cooperation between archaeological studies and molecular analysis allows us to contribute to clarifying the economic strategies for a Central Italian community in a scenario that is still poor in published data

The Role of Anti-Müllerian Hormone in the Characterization of the Different Polycystic Ovary Syndrome Phenotypes

Rotterdam criteria identified 4 polycystic ovary syndrome (PCOS) phenotypes based on the combination of anovulation (ANOV), hyperandrogenism (HA), and polycystic ovaries (PCOs): phenotype 1 (ANOV + HA + PCO), phenotype 2 (ANOV + HA), phenotype 3 (HA + PCO), and phenotype 4 (ANOV + PCO). Anti-Müllerian hormone (AMH) was suggested to play a pathophysiologic and diagnostic role in this syndrome. The aim of this study was to compare AMH levels among the different phenotypes in relation to clinical, endocrine, and metabolic features. We enrolled 117 women with PCOS (body mass index: 25.89 ± 6.20 kg/m(2), age range: 18-37 years) and 24 controls. Anthropometric characteristics, hirsutism score, ultrasound ovarian features, and hormonal parameters, including AMH, were evaluated. Each participant also underwent an oral glucose tolerance test and an euglycemic-hyperinsulinemic clamp. The prevalence of phenotypes 1 to 4 was 62.4%, 8.6%, 11.1%, and 17.9%, respectively. Body mass index and insulin resistance indexes were similar among the groups. Phenotype 1 showed the highest luteinizing hormone, androgens levels, ovarian volume, and AMH concentrations (9.27 ± 8.17 ng/mL,P&lt; .05) versus phenotype 2 and controls. Phenotype 2 women were hirsute, showed an intermediate free androgen index value, low ovarian volume, and low AMH levels (4.05 ± 4.12 ng/mL). Phenotype 3 showed an intermediate state of HA and slightly augmented AMH levels (5.87 ± 4.35 ng/mL). The clinical and endocrine characteristics of phenotype 4 resembled those of controls, except for higher ovarian volume and AMH levels (7.62 ± 3.85 ng/mL;P&lt; .05). Our results highlight the heterogeneity of the association between increased AMH levels, menstrual dysfunction, and HA in the different PCOS phenotypes, thus offering a key to an understanding of the current controversy on the value of AMH measurement in PCOS

Expectant management may reduce overtreatment in women affected by unexplained infertility confirmed by diagnostic laparoscopy.

PURPOSE: To determine whether the mini-invasive surgery still play a role in the diagnostic workup and in the management of the couples affected by unexplained infertility. METHODS: 170 infertile women (age range 25-38 years) with documented normal ovarian, tubal and uterine function underwent combined hysteroscopic and laparoscopic surgery; 100 women refused surgery or ART treatment (control group) choosing expectant management. A retrospective assessment questionnaire was proposed to enrolled women to collect the rate of spontaneous or ART-induced pregnancies. RESULTS: The combined surgery revealed pelvic pathologies in 49.4% of patients, confirming the diagnosis of unexplained infertility only in 86 of studied patients. In this group of 86 selected women, 28 of them achieved a spontaneous pregnancy and 23 women obtained pregnancy after ART. The Chi-square analysis shows that the pregnancy rate was not influenced by the employment of ART. In the group of 100 control women, only 14 (14%) achieved a spontaneous pregnancy after 18 months of expectant management. CONCLUSIONS: Combined laparoscopy and hysteroscopy in women with unexplained infertility may reveal previously undiagnosed pathologies that could require ART, and in those without abnormal surgical finding, ART does not improve pregnancy rate