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Background: Lactose intolerance is the most frequent food intolerance, but many subjects with self-reported milk intolerance (SRMI) are asymptomatic at lactose hydrogen breath test (LHBT). The aim of this study was to evaluate the frequency of lactose intolerance in SRMI patients and their clinical characteristics. Methods: In a retrospective study, the clinical records of 314 SRMI patients (259 females, mean age: 39.1 ± 13.5 years) were reviewed; 102 patients with irritable bowel syndrome (IBS) served as controls. In a prospective study, 42 SRMI patients, negatives at the LHBT, underwent a double-blind, placebo-controlled (DBPC) whole cow’s milk challenge. Results: In the retrospective study, only 178 patients (56%) were lactose maldigesters and intolerant at LHBT; 68% of the subjects with SRMI were suffering from IBS; 74% reported dyspepsia (p = 0.0001 vs. IBS controls); and weight loss was recorded in 62 SRMI patients (20%) (p = 0.01 vs. IBS controls). Duodenal histology showed intra-epithelial lymphocytosis in about 60% of cases. In the prospective study, 36 patients (86%) experienced symptoms during the DBPC cow’s milk challenge, and only 4 patients (9%) reacted to placebo (p = 0.0001). Conclusions: A percentage of SRMI patients were not suffering from lactose intolerance. DBPC revealed that SRMI patients had clinical reactions when exposed to whole cow’s milk.

Background: Lactose intolerance is the most frequent food intolerance, but many subjects with self-reported milk intolerance (SRMI) are asymptomatic at lactose hydrogen breath test (LHBT). The aim of this study was to evaluate the frequency of lactose intolerance in SRMI patients and their clinical characteristics. Methods: In a retrospective study, the clinical records of 314 SRMI patients (259 females, mean age: 39.1 ± 13.5 years) were reviewed; 102 patients with irritable bowel syndrome (IBS) served as controls. In a prospective study, 42 SRMI patients, negatives at the LHBT, underwent a double-blind, placebo-controlled (DBPC) whole cow’s milk challenge. Results: In the retrospective study, only 178 patients (56%) were lactose maldigesters and intolerant at LHBT; 68% of the subjects with SRMI were suffering from IBS; 74% reported dyspepsia (p = 0.0001 vs. IBS controls); and weight loss was recorded in 62 SRMI patients (20%) (p = 0.01 vs. IBS controls). Duodenal histology showed intra-epithelial lymphocytosis in about 60% of cases. In the prospective study, 36 patients (86%) experienced symptoms during the DBPC cow’s milk challenge, and only 4 patients (9%) reacted to placebo (p = 0.0001). Conclusions: A percentage of SRMI patients were not suffering from lactose intolerance. DBPC revealed that SRMI patients had clinical reactions when exposed to whole cow’s milk.

Background Nutritional status and sarcopenia are established contributors to morbidity and mortality in chronic respiratory diseases. This study aimed to assess the prevalence and impact of body composition features extracted from computed tomography (CT) in patients with non-CF bronchiectasis. Methods We analysed data from 112 patients. Muscle and subcutaneous fat area and density were assessed by semi-automatic segmentation at the level of the 12th thoracic vertebra using the mediastinal window of routine chest CT scans. Clinical and functional features were compared between patients with and without body composition abnormalities. Associations between CT-derived body composition parameters and clinical outcomes were explored. Results The majority of patients were female (86/112, 77%) and the median age was 66 years (56–74). Myosteatosis (low muscle density) affected 75 of 112 (66%) patients. Patients with myosteatosis (MSp) were older than those without (wMSp), median age 70 (61–77) vs. 58 (45–69) years ( p  < 0.001), and had lower FEV 1 , 81 (69–95) vs. 89 (78–101) % pred. ( p  = 0.038) and MEF 50 , 48 (25–66) vs. 61 (44–74) % pred. ( p  = 0.043). The incidence of non-tuberculous mycobacteria (NTM) pulmonary disease was higher in MSp compared to wMSp (19% vs. 3%; p  = 0.043). Muscular density negatively correlated with the Bronchiectasis Severity Index ( r  = − 0.32; p  = 0.012), FACED ( r  = − 0.38; p  = 0.03) and E-FACED ( r  = − 0.35; p  = 0.007) scores. Myosteatosis was not related to gender, radiological extension of bronchiectasis, bacterial colonization or laboratory data. Conclusions Myosteatosis is highly prevalent in patients with bronchiectasis and is associated with worse airflow obstruction, higher disease severity, and increased frequency of NTM pulmonary disease, independently from BMI. Abnormal body composition as defined by CT assessment may provide clinically relevant information beyond traditional anthropometrics and complement existing severity scores for risk stratification in patients with bronchiectasis.

Low values of the ratio of plasmatic soluble blocking factor FMS-like tyrosine Kinase 1 and placental growth factor (sFlt-1/PlGF) are required for an adequate placental angiogenesis and function. It has been shown that patients affected by gestational diabetes (GD) and patients with pneumonia from SARS-CoV-2 are characterized by an increased sFlt-1/PlGF ratio. The aim of the present study was to evaluate the sFlt-1-PlGF ratio in pregnancies complicated by COVID-19 and GD. We compared the plasmatic sFlt-1/PlGF ratio among the following groups of pregnant women: COVID-19, GD patients; COVID-19, non-GD patients; non-COVID-19, GD patients; and non-COVID-19, non-GD controls. We enrolled 62 women in the present study, who were divided as follows: 14 COVID-19, GD patients; 12 COVID-19, non-GD patients; 11 non-COVID-19, GD patients; and 25 non-COVID-19, non-GD controls. The COVID-19, GD patients presented a higher pre-pregnancy BMI, a higher prevalence of hypertensive disorders of pregnancy as a co-morbidity, and an increased need for medication for their diabetes. Neonatal data were similar between the groups. The controls showed a significantly lower sFlt-1/PlGF ratio compared to pregnancies complicated by GD and SARS-CoV-2 infection. The sFlt-1/PlGF ratio was higher in patients affected by both GD and SARS-CoV-2 infection; these subjects were characterized by a greater incidence of obesity and hypertensive disorders of pregnancy.

Background It is known that tissue macrophages derive not only from blood monocytes but also from yolk sac or fetal liver, and the tissue of residence guides their function. When isolated, they lose tissue specific signatures, hence studies of human macrophages should be ideally done directly in the tissue. The aim of this study was to investigate directly in human lung tissue the polarization of alveolar macrophage (AM), classic (M1) or alternative (M2), in health and disease, using COPD as a model. Methods Surgical lungs from 53 subjects were studied: 36 smokers whose FEV 1 varied from normal to severe COPD, 11 non-smokers and 6 normal donors. iNOS and CD206 immunohistochemistry was used to quantify the percentage of AM polarized as M1 or M2 in lung sections. Results and Discussion The percentage of M1 and M2 increased progressively with smoking and COPD severity, from 26% to 84% for M1 and from 7% to 78% for M2. In donors 74% of AM were negative for M1 and 93% for M2. Confocal microscopy showed co-localization of M1 and M2 in the same AM in severe COPD. Conclusion In normal lungs alveolar macrophages were mostly non-polarized. With smoking and COPD severity, M1 and M2 polarization increased significantly and so did the co-expression of M1 and M2 in the same alveolar macrophage.

In this work, we have analysed the binding of the Pt(II) complexes ([PtCl(4′-phenyl-2,2′:6′,2″-terpyridine)](CF3SO3) (1), [PtI(4′-phenyl-2,2′:6′,2″-terpyridine)](CF3SO3) (2) and [PtCl(1,3-di(2-pyridyl)benzene) (3)] with selected model proteins (hen egg-white lysozyme, HEWL, and ribonuclease A, RNase A). Platinum coordination compounds are intensively studied to develop improved anticancer agents. In this regard, a critical issue is the possible role of Pt-protein interactions in their mechanisms of action. Multiple techniques such as differential scanning calorimetry (DSC), electrospray ionization mass spectrometry (ESI-MS) and UV-Vis absorbance titrations were used to enlighten the details of the binding to the different biosubstrates. On the one hand, it may be concluded that the affinity of 3 for the proteins is low. On the other hand, 1 and 2 strongly bind them, but with major binding mode differences when switching from HEWL to RNase A. Both 1 and 2 bind to HEWL with a non-specific (DSC) and non-covalent (ESI-MS) binding mode, dominated by a 1:1 binding stoichiometry (UV-Vis). ESI-MS data indicate a protein-driven chloride loss that does not convert into a covalent bond, likely due to the unfavourable complexes’ geometries and steric hindrance. This result, together with the significant changes of the absorbance profiles of the complex upon interaction, suggest an electrostatic binding mode supported by some stacking interaction of the aromatic ligand. Very differently, in the case of RNase A, slow formation of covalent adducts occurs (DSC, ESI-MS). The reactivity is higher for the iodo-compound 2, in agreement with iodine lability higher than chlorine.

Poultry feathers are among the most abundant and polluting keratin-rich waste biomasses. In this work, we developed a one-pot microwave-assisted process for eco-friendly keratin extraction from poultry feathers followed by a direct electrospinning (ES) of the raw extract, without further purification, to obtain keratin-based bioplastics. This microwave-assisted keratin extraction (MAE) was conducted in acetic acid 70% v/v. The effects of extraction time, solvent/feathers ratio, and heating mode (MAE vs. conventional heating) on the extraction yield were investigated. The highest keratin yield (26 ± 1% w/w with respect to initial feathers) was obtained after 5 h of MAE. Waste-derived keratin were blended with gelatin to fabricate keratin-based biodegradable and biocompatible bioplastics via ES, using 3-(Glycidyloxypropyl)trimethoxysilane (GPTMS) as a cross-linking agent. A full characterization of their thermal, mechanical, and barrier properties was performed by differential scanning calorimetry, thermogravimetric analysis, uniaxial tensile tests, and water permeability measurements. Their morphology and protein structure were investigated using scanning electron microscopy and attenuated total reflection-infrared spectroscopy. All these characterizations highlighted that the properties of the keratin-based bioplastics can be modulated by changing keratin and GPTMS concentrations. These bioplastics could be applied in areas such as bio-packaging and filtration/purification membranes.

Silicosis caused by the inhalation/deposition of free silica particles is characterized by pulmonary inflammation/fibrosis. Among the clinical disorders associated with silicosis, tuberculosis is by far the most prominent. A 66-year-old male non-smoker, originally from North Africa, reported a dry cough and significant weight loss. He was a foundry worker. He had a medical history of bladder carcinoma associated with schistosomiasis. Computed tomography (CT) and positron emission tomography (PET)/CT showed bilateral multiple hypermetabolic lung nodules, some with cavitation. The patient underwent surgical resection of the largest nodule, which was highly suspicious of lung metastasis. The histological examination revealed multiple nodular formations. Several lesions showed the characteristic features of silicotic nodules. There were also adjacent well-formed granulomas, some with central caseous necrosis. A real-time polymerase chain reaction, performed for the identification and quantification of the DNA of the Mycobacterium tuberculosis complex, was positive. Pulmonary silico-tuberculosis is often encountered in patients with a history of silica exposure in tuberculosis-endemic areas. This case serves as a reminder to never underestimate patient occupational exposure and geographic origin. A careful histological diagnosis and molecular investigation are mandatory when approaching difficult cases, especially patients with a prior cancer history and clinical/radiological features suggestive of tumour recurrence/metastasis.

Abstract Background Patients with deficient mismatch repair (dMMR) and/or microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) show marked sensitivity to immune checkpoint inhibitors (ICIs). Dual PD-1/CTLA-4 blockade with nivolumab and ipilimumab showed superior progression-free survival (PFS) over chemotherapy and anti-PD-1 monotherapy, but data on treatment-naïve patients is not available yet. Methods This international multicenter study included patients with dMMR/MSI-H mCRC receiving either chemotherapy with or without biologics, or anti-PD-1 monotherapy, or dual PD-1/CTLA-4 blockade as a first-line treatment. Data were adjusted using inverse probability of treatment weighting (IPTW) to account for baseline imbalances. IPTW-adjusted survival and subgroup analyses were conducted. Results Among 711 patients, 51.2% received chemotherapy with or without biologics, 37.1% anti-PD-1 monotherapy, and 11.7% dual checkpoint blockade. Anti-CTLA-4 combination therapy significantly improved PFS (HR: 0.14; P < .001) and OS (HR: 0.13; P < .001) vs chemotherapy. In first-line IPTW-adjusted analyses (median follow-up: 29.2 months), dual blockade showed superior PFS over PD-1 monotherapy (HR: 0.58, 95% CI, 0.35-0.97, P = .037), with a favorable OS trend (HR: 0.61, 95% CI, 0.33-1.14, P = .12), and higher objective response rate (ORR) (71.5% vs 55.5%; OR: 1.15; 95% CI, 1.03-1.29; P = .016) and disease control rate (DCR) (93.7% vs 75.8%; OR, 1.18; 95% CI, 1.08-1.28; P < .001). Subgroup analyses suggested greater benefit in patients with left-sided and BRAF mutated tumors, while those with right-sided BRAF wild-type status showed no incremental benefit from dual ICI. Toxicity profile was manageable for both ICI regimen, with grade 3 or 4 immune-related adverse events registered in 11.9% and 15.7% cases in anti-PD-1 monotherapy and anti-CTLA-4 combination groups, respectively. Conclusions First-line dual PD-1/CTLA-4 blockade demonstrated superior efficacy over anti-PD-1 monotherapy in dMMR/MSI-H mCRC regardless of clinical variables. Compared to previous published data across treatment lines, the prognostic impact of several clinical features does not seem to be retained in patients treated upfront with ICIs combination.

Over the years, several materials have been used for restoration purposes, with different types of dyes and colour hues. Recently, some researchers have proposed geopolymers (GPs) or amorphous aluminosilicate polymers for these purposes. In this work, an alcohol-based grape marc extract (GME, obtained via dark maceration assisted with ultrasound) was used as a natural dyeing agent for metakaolin-based GPs. The geopolymerisation occurrence was assessed by Fourier-transform infrared (FT-IR) spectroscopy and X-ray diffraction analysis, while the colour of the resulting material was determined through the colorimetric analysis in the L * a * b * colour space. Additionally, the thermal stability of GME and GPs was investigated by thermogravimetry coupled with FT-IR spectroscopy. The microstructure, the reticulation stability, and the antimicrobial activity of GPs were examined through the scanning electron microscopy, the pH and ionic conductivity measurements, integrity, and mass loss tests. Overall, a coloured geopolymer with suitable thermal, antimicrobial, and mechanical properties was obtained, justifying its potential use in restoration or, more generally, in the construction field. Graphical abstract