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Low-molecular-weight peptide gelators are a versatile class of compounds able to form gels under a variety of conditions, even via simple ultrasound sonication. In this paper, the ability of Boc-L-Phe-D-Oxd-L-Phe-OBn to gelate three organic solvents (toluene, tert-butyl methyl ether, and ethanol) was evaluated. The rheological behaviour of the materials was assessed via strain sweep analysis, while the fibrous network was analysed via optical microscopy on the wet gels. The gel obtained from toluene is a highly transparent material, and the one from ethanol appears translucent, while the one from tert-butyl methyl ether is opaque. These gels were used to study the reversible light-induced transformation from spyropiran (SP) to merocyanine (MC) and back, as a model system to check the effect of the gel medium onto the rection kinetic. We observed that the solvent used to form the organogels has a crucial effect on the reaction, as gels from aprotic solvents stabilize the SP form, while the ones from protic solvents stabilize the MC form. We thus obtained a solid support to stabilize the two photochromic species just by changing the solvent polarity. Moreover, we could demonstrate that the self-assembled gels do not interfere with the light-driven conversion process, either starting from SP or MC, thus representing a valid and economical photochromic material. [ABSTRACT FROM AUTHOR]

Background: Available data on Mismatch Repair system (MMR) deficiency are conflicting and derived from small studies. Our study aimed to evaluate the therapeutic implications of MMR status in patients with locally advanced rectal cancer (LARC). Methods: We retrospectively collected data from 318 patients affected by LARC treated in Italy at the Medical Oncology Units of the University Hospital of Cagliari, Istituto Nazionale dei Tumori Milan, and AOU Ospedali Riuniti Ancona. All patients underwent neoadjuvant chemoradiotherapy. The primary objective was major TRG while secondary objectives were pathological complete response, disease-free survival (DFS) and overall survival (OS). Results: One hundred sixty patients (148 pMMR and 12 dMMR) were included in the exploratory cohort and 158 (146 pMMR and 12 dMMR) were included in the validation cohort. A major TRG has been shown in 42.6% and 43.1% patients with pMMR in exploratory and validation cohort, respectively; while no major TRG have been shown in dMMR patients in both cohorts. Exploratory and validation cohorts showed a statistically significant higher mDFS in pMMR patients compared to dMMR: NR vs. 14 months and NR vs. 17 months, respectively. Conclusion: Our results indicated an association between dMMR and poor response to preoperative chemoradiotherapy and they represent a hypothesis-generating data for new neoadjuvant strategies. [ABSTRACT FROM AUTHOR]

Low‐molecular‐weight hydrogels are made of a small percentage of small organic molecules dispersed in an aqueous medium, which may aggregate in several manners using different methods. However, often the organic gelator in water has poor solubility, so the addition of a solubilising agent is required. In the case of acidic gelators, this mainly consists of the addition of a strong base, that is sodium hydroxide, that deprotonates the acidic moiety, so the gelator molecules become more soluble and tend to assemble into micelles, forming a dispersion. Some gelators, however, are sensitive to the harsh pH and get hydrolysed. This is the case of some molecules presenting carbamates in their features, like Fmoc‐protected or oxazolidinone‐containing peptides. In this paper, we present a valid alternative to sodium hydroxide, by dissolving a tripeptide containing an oxazolidinone moiety in a phosphate buffer (PB) medium at pH 7.4. The results obtained with the NaOH dissolution are compared with the ones with PB, as both methods present advantages and drawbacks. The use of NaOH produces transparent but weak hydrogels, as it exposes the gelator to harsh conditions that end up in its partial hydrolysis, which is more pronounced at high concentrations (≥10 mM). Using PB to dissolve the gelator, this problem is completely avoided as no hydrolysis product has been detected in the hydrogels, which are very stiff although more opaque. By tuning the preparation conditions, we can obtain a wide variety of hydrogels, with the properties required by the final application. [ABSTRACT FROM AUTHOR]

Supramolecular and biocompatible hydrogels with a tunable pH ranging from 5.5 to 7.6 lead to a wide variety of formulations useful for many different topical applications compatible with the skin pH. An in vitro viability/cytotoxicity test of the gel components demonstrated that they are non-toxic, as the cells continue to proliferate after 48 h. An analysis of the mechanical properties demonstrates that the hydrogels have moderate strength and an excellent linear viscoelastic range with the absence of a proper breaking point, confirmed with thixotropy experiments. Two cosmetic active peptides (Trifluoroacetyl tripeptide-2 and Palmitoyl tripeptide-5) were successfully added to the hydrogels and their transdermal permeation was analysed with Franz diffusion cells. The liquid chromatography-mass spectrometry (HPLC-MS) analyses of the withdrawn samples from the receiving solutions showed that Trifluoroacetyl tripeptide-2 permeated in a considerable amount while almost no transdermal permeation of Palmitoyl tripeptide-5 was observed. [ABSTRACT FROM AUTHOR]

We use a pH‐driven annealing process to convert between co‐assembled and self‐sorted networks in multicomponent gels. The initially formed gels at low pH are co‐assembled, with the two components coexisting within the same self‐assembled structures. We use an enzymatic approach to increase the pH, resulting in a gel‐to‐sol transition, followed by a hydrolysis to lower the pH once again. As the pH decreases, a self‐sorted network is formed by a two‐stage gelation process determined by the pKa of each component. This approach can be expanded to layered systems to generate many varied systems by changing composition and rates of pH change, adapting their microstructure and so allowing access to a far greater range of morphologies and complexity than can be achieved in single component systems. [ABSTRACT FROM AUTHOR]

We use a pH‐driven annealing process to convert between co‐assembled and self‐sorted networks in multicomponent gels. The initially formed gels at low pH are co‐assembled, with the two components coexisting within the same self‐assembled structures. We use an enzymatic approach to increase the pH, resulting in a gel‐to‐sol transition, followed by a hydrolysis to lower the pH once again. As the pH decreases, a self‐sorted network is formed by a two‐stage gelation process determined by the pKa of each component. This approach can be expanded to layered systems to generate many varied systems by changing composition and rates of pH change, adapting their microstructure and so allowing access to a far greater range of morphologies and complexity than can be achieved in single component systems. [ABSTRACT FROM AUTHOR]

Controlling the formation and directional growth of hydrogels is a challenge. In this paper, a new methodology to program the gel formation both over space and time is proposed, using the diffusion and subsequent hydrolysis of 1,1′‐carbonyldiimidazole from an immiscible organic solution to the aqueous gel media. [ABSTRACT FROM AUTHOR]

The removal of Diclofenac sodium from waste waters has a high relevance since it belongs to the therapeutic group most commonly found in wastes. An aromatic‐free and low‐impact technology that efficiently entraps aqueous pollutants is highly desirable. We synthesised two Boc‐protected and aromatic‐free tripeptides (Boc‐L‐Ala‐Aib‐L‐Val‐OH and Boc‐L‐Val‐Aib‐L‐Val‐OH) and studied their ability to form gels with mixtures of water and alcohols, such as methanol, ethanol and 2‐propanol. Boc‐L‐Ala‐Aib‐L‐Val‐OH forms a strong hydrogel in 2‐propanol/water mixtures able to trap up to 97.8% of Eosin Y model molecule and up to 92.0% of Diclofenac sodium from aqueous solutions. The hydrogel is also thixotropic, thermoreversible and biocompatible. This outcome is very encouraging and paves the way to a new approach for developing new materials using aromatic‐free hydrogels, useful for water remediation. [ABSTRACT FROM AUTHOR]

Imines or Schiff bases (SB) are formed by the condensation of an aldehyde or a ketone with a primary amine, with the removal of a water molecule. Schiff bases are central molecules in several biological processes for their ability to form and cleave by small variation of the medium. We report here the controlled hydrolysis of four SBs that may be applied in the fragrance industry, as they are profragrances all containing odorant molecules: methyl anthranilate as primary amine, and four aldehydes (cyclamal, helional, hydroxycitronellal and triplal) that are very volatile odorants. The SB stability was assessed over time by HPLC-MS in neutral or acidic conditions, both in solution and when trapped in low molecular weight gels. Our results demonstrate that it is possible to control the hydrolysis of the Schiff bases in the gel environment, thus tuning the quantity of aldehyde released and the persistency of the fragrance. [ABSTRACT FROM AUTHOR]

The ability of mussels to adhere to underwater surfaces has attracted a lot of attention from the scientific community. As proteins containing L‐DOPA (3,4‐dihydroxyphenyl‐l‐alanine) are involved in their adhesion, a common strategy to synthesize adhesives is the incorporation of this amino acid into other compounds. Herein, we report a study on four compounds of the family of Bocx‐(L‐DOPA)n‐OMe (x = 1–3; n = 1,2), that we prepared through simple synthetic steps. Three of them showed the capability of underwater adhesion: while they are not adhesive in the dry phase, the adhesiveness is triggered when the dried sample is immersed in water or any aqueous solutions. The introduction of protecting groups stabilizes L‐DOPA, preventing the oxidation of the catechol moiety, and enhances the hydrophobicity, helping the removal of water from the surface to bind. These molecules show good adhesiveness, with different properties, so they may be all used as adhesives for different purposes. These outcomes pave the way for new applications for these materials as green and biocompatible adhesives. [ABSTRACT FROM AUTHOR]

Allergic contact dermatitis to braces containing 4,4'-diaminodiphenylmethane, a previously unreported causative agent Keywords: allergic contact dermatitis; brace; case report; diaminodiphenylmethane; orthopedic support EN allergic contact dermatitis brace case report diaminodiphenylmethane orthopedic support 157 159 3 07/27/20 20200801 NES 200801 4,4'-Diaminodiphenylmethane (4,4'-MDA, CAS no. 101-77-9), an aromatic amine, is the degradation product of 4,4'-methylenebis(phenyl isocyanate) (4,4'-MDI). The patient had had a fracture of the fifth right metatarsal bone 20 days prior and had been wearing a leg brace made of polyurethane ever since (Figure 1A). [Extracted from the article]

CD31 reactivity is generally utilized as a marker of endothelial cells. CD31 immunoreactivity in the developing human kidney revealed that fetal glomerular capillary endothelial cells change their immunohistochemical phenotype during maturation. The aim of this study was to analyze CD31 reactivity in the fetal human kidney in the different stages of intrauterine development: We observed different distribution of CD31-reactive vascular progenitors in the different areas of the developing kidney. In particular, the nephrogenic zone and the renal capsule were characterized by a scarcity of CD31-reactive cells at all gestational ages. These data suggest the hypothesis that nephrogenesis does not need high oxygen levels and confirms a major role of hypoxia in nephrogenesis. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the accuracy of liver biopsy findings in preoperative assessment of chemotherapyassociated liver injuries (CALIs). Design: Prospective study. Setting: Tertiary care referral hospital. Patients: From July 1, 2007, to January 31, 2011, all patients with colorectal metastases receiving preoperative oxaliplatin- and/or irinotecan-based chemotherapy (⩾4 cycles) were considered for the present study. Patients underwent parenchymal biopsy before liver resection. Blinded CALI evaluation was performed on biopsy and resection specimens. Intervention: Liver resection. Main Outcome Measures: Sensitivity, specificity, and accuracy of liver biopsy in CALI evaluation. Results: We included 100 patients. At specimen analysis, grade 2or 3 steatosis was diagnosed in 30 patients; grade 2 or 3 sinusoidal dilatation, in 28; grade 2 hepatocellular ballooning, in 3; grade 2 or 3 lobular inflammation, in 25; and steatohepatitis in 19. Obesity was associated with grade 3 steatosis (20.8% vs 5.3%; odds ratio [OR], 4.74 [P=.03]) and steatohepatitis (33.3% vs 14.5%; OR, 2.96 [P=.04]). Oxaliplatin administration was associated with higher sinusoidal dilatation grade (P=.049). Mortality (2 cases) was increased among patients with steatohepatitis (10.5% vs 0; OR, 13.67 [P=.04]). Biopsy findings correctly predicted steatosis (sensitivity, 88.9%; accuracy, 93.0%) but had low sensitivity and accuracy for sinusoidal dilatation (21.4% and 63.0%, respectively), hepatocellular ballooning (16.0% and 69.0%, respectively), lobular inflammation (20.0% and 78.0%, respectively), and steatohepatitis (21.1% and 79.0%, respectively). Biopsy accuracy did not improve regarding specific chemotherapy regimens or prolonged treatments. Conclusions: Liver biopsy cannot be considered a reliable tool in assessing CALIs except for steatosis. The procedure should not be recommended during preoperative workup. [ABSTRACT FROM AUTHOR]

Cytologic findings of glandular lesions of the cervix uteri are often difficult to evaluate. We studied the usefulness of CINtec PLUS p16/Ki-67 double stain (mtm laboratories, Heidelberg, Germany) for the diagnosis of glandular lesions. The study included 47 abnormal results on liquid-based cytologic tests with a subsequent histologic diagnosis of adenocarcinoma in situ or with early invasion, and 16 samples with negative results on follow-up. All samples were stained with CINtec PLUS p16/Ki-67 double stain. Of the neoplastic samples, 7 were excluded because of insufficient residual cellularity or loss of neoplastic cells. Of the samples that were adequate, 92.5% were stained with CINtec PLUS, whereas 7.5% were judged inconclusive. All inconclusive cases were at least 3 years old. Of the 16 negative samples, 15 (93.8%) stained negative and only 1 (6.2%) showed several positive clusters of cells. Our study shows that CINtec PLUS is a robust and useful tool for the diagnosis of glandular lesions of the cervix uteri. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the accuracy of liver biopsy findings in preoperative assessment of chemotherapy associated liver injuries (CALIs). Design: Prospective study. Setting: Tertiary care referral hospital. Patients: From July 1, 2007, to January 31, 2011, all patients with colorectal metastases receiving preoperative oxaliplatin- and/or irinotecan-based chemotherapy (⩾4 cycles) were considered for the present study. Patients underwent parenchymal biopsy before liver resection. Blinded CALI evaluation was performed on biopsy and resection specimens. Intervention: Liver resection. Main Outcome Measures: Sensitivity, specificity, and accuracy of liver biopsy in CALI evaluation. Results: We included 100 patients. At specimen analysis, grade 2or 3 steatosis was diagnosed in 30 patients; grade 2 or 3 sinusoidal dilatation, in 28; grade 2 hepatocellular ballooning, in 3; grade 2 or 3 lobular inflammation, in 25; and steatohepatitis in 19. Obesity was associated with grade 3 steatosis (20.8% vs 5.3%; odds ratio [OR], 4.74 [P=.03]) and steatohepatitis (33.3% vs 14.5%; OR, 2.96 [P=.04]). Oxaliplatin administration was associated with higher sinusoidal dilatation grade (P=.049). Mortality (2 cases) was increased among patients with steatohepatitis (10.5% vs 0; OR, 13.67 [P=.04]). Biopsy findings correctly predicted steatosis (sensitivity, 88.9%; accuracy, 93.0%) but had low sensitivity and accuracy for sinusoidal dilatation (21.4% and 63.0%, respectively), hepatocellular ballooning (16.0% and 69.0%, respectively), lobular inflammation (20.0% and 78.0%, respectively), and steatohepatitis (21.1% and 79.0%, respectively). Biopsy accuracy did not improve regarding specific chemotherapy regimens or prolonged treatments. Conclusions: Liver biopsy cannot be considered a reliable tool in assessing CALIs except for steatosis. The procedure should not be recommended during preoperative workup. [ABSTRACT FROM AUTHOR]

Background: The optimal duration, safety, and benefit of preoperative chemotherapy in patients with colorectal liver metastases (CLM) are unclear. We evaluated the association between the duration of preoperative chemotherapy with 5-fluorouracil (5-FU), leucovorin, oxaliplatin (FOLFOX) ± bevacizumab, pathologic response, and hepatotoxicity after hepatic resection for CLM. Methods: A total of 219 patients underwent hepatic resection following FOLFOX with or without bevacizumab and were divided into 2 groups according to the chemotherapy duration: 1-8 cycles (short duration [SD]; N = 157) and ≥9 cycles (long duration [LD]; N = 62). The frequency of complete or major pathologic response, sinusoidal injury, and major postoperative morbidity were compared. Results: Treatment consisting of ≥9 cycles was not associated with an increase in complete or major pathologic response (SD vs. LD, 57% vs. 55%; P = .74). The incidence of sinusoidal injury was higher in the LD group (26% vs. 42%; P = .017). The incidence of liver insufficiency was higher in the LD group (4% vs. 11%; P = .035). Sinusoidal injury did not predict postoperative liver insufficiency; multivariate analysis revealed ≥9 cycles was the only independent predictor of postoperative liver insufficiency ( P = .031; odds ratio = 3.90). Chemotherapy including bevacizumab was associated with a significantly higher frequency of complete or major response in both SD and LD groups. Conclusions: Extended preoperative chemotherapy increases the risk of hepatotoxicity in CLM without improving the pathologic response. The type of chemotherapy (FOLFOX with bevacizumab) has more impact on pathologic response than the duration of chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Chronic atrophic gastritis (CAG) is a precursor of the intestinal type of gastric cancer, the second leading cause of cancer-related death worldwide. GastroPanel is a recently marketed serological kit for the non-invasive diagnosis of CAG, defined by some authors 'even more reliable than biopsy histology'. The goal of this study was 1) to evaluate the agreement between the serum gastric profile provided by GastroPanel (PGI, PGII, G-17, AbHp) and histology over CAG diagnosis, and 2) to evaluate the prevalence of CAG by means of GastroPanel in a Northern Italian dyspeptic population. Methods: Basal blood samples for GastroPanel parameters evaluation (Biohit Plc, Finland) were collected after an overnight fast from 1387 dyspeptic patients (age range: 18-80 years; F 704). Gastroscopy with two biopsies each of the antrum and corpus was offered to a group of the first 400 consecutive patients (age 18-80 years, F 214) to compare the results of histology and GastroPanel in CAG. Results: Agreement between GastroPanel and histology for corpus-prevalent CAG was 94%, with a sensitivity and specificity of 80% and 96%, respectively. In our series of 1387 dyspeptic patients, the prevalence of corpus-prevalent CAG, of antral-prevalent CAG and of multifocal CAG (antrum+ corpus) was 10.7%, 3.6% and 2.4%, respectively. Out of the 34 patients with multifocal atrophic gastritis, 12% were under 30 years of age. Conclusions: GastroPanel is a reliable non-invasive test for diagnosis of CAG and deserves consideration for current use in clinical practice as a valuable diagnostic tool. Clin Chem Lab Med 2010;48:1327-32. [ABSTRACT FROM AUTHOR]

The study aim is to evaluate the efficacy and safety of two low-dose vaginal estrogen treatments (ETs) and of a non-hormonal vaginal moisturizer in postmenopausal breast cancer survivors with urogenital atrophy. Eighteen patients receiving estriol cream 0.25 mg ( n = 10) or estradiol tablets 12.5 μg ( n = 8) twice/week for 12 weeks were evaluated and compared with eight patients treated with polycarbophil-based moisturizer 2.5 g twice/week. Severity of vaginal atrophy was assessed using subjective [Vaginal Symptoms Score (VSS), Profile of Female Sexual Function (PFSF)] and objective [Vaginal Health Index (VHI), Karyopycnotic Index (KI)] evaluations, while safety by measuring endometrial thickness and serum sex hormones levels. After 4 weeks, VSS and VHI were significantly improved by both vaginal ETs, with further improvement after 12 weeks. PFSF improved significantly only in estriol group ( p = 0.02). Safety measurements did not significantly change. Vaginal moisturizer improved VSS at week 4 ( p = 0.01), but score returned to pre-treatment values at week 12; no significant modification of VHI, KI, PFSF was recorded. Both low-dose vaginal ET are effective for relieving urogenital atrophy, while non-hormonal moisturizer only provides transient benefit. The increase of serum estrogens levels during treatment with vaginal estrogen at these dosages is minimal. [ABSTRACT FROM AUTHOR]

Zinc is the second most abundant trace element in the human body, and it plays a fundamental role in human physiology, being an integral component of hundreds of enzymes and transcription factors. The discovery that zinc atoms may compete with copper for their absorption in the gastrointestinal tract let to introduce zinc in the therapy of Wilson's disease, a congenital disorder of copper metabolism characterized by a systemic copper storage. Nowadays, zinc salts are considered one of the best therapeutic approach in patients affected by Wilson's disease. On the basis of the similarities, at histological level, between Wilson's disease and non-alcoholic liver disease, zinc has been successfully introduced in the therapy of non-alcoholic liver disease, with positive effects both on insulin resistance and oxidative stress. Recently, zinc deficiency has been indicated as a possible factor responsible for the susceptibility of elderly patients to undergo infection by SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic. Here, we present the data correlating zinc deficiency with the insurgence and progression of Covid-19 with low zinc levels associated with severe disease states. Finally, the relevance of zinc supplementation in aged people at risk for SARS-CoV-2 is underlined, with the aim that the zinc-based drug, classically used in the treatment of copper overload, might be recorded as one of the tools reducing the mortality of COVID-19, particularly in elderly people. [ABSTRACT FROM AUTHOR]

In order to evaluate clinical and psychosocial results of isolated coronary artery by-pass graft (CABG) we studied 626 consecutive patients, mean age 61 +/- 8 years (86% men), in a follow-up (median: 58 months) with a complete questionnaire about cardiosurgical problems (post-operative vital status, angina relapse, infarction, heart failure, PTCA, redo, PM) and psychosocial variables (mood, irritableness, job satisfaction, hobby satisfaction, family relations, sexual activity, general well-being and work status). Global evaluation improvement of psychosocial variables was found in 71% of patients without cardiac events (group A) and 11% of patients with cardiac events (group B); worsening was found in 2% of group A and 1% of group B; no referred variations in 13% and 2% respectively (p < or = 0.05. Interests (in work, hobbies and sexual activities) demonstrate an improvement in 20% (group A) and 2% (group B); worsening in 12% (group A) and 4% (group B); no variations in 51% (group A) and 11% (group B) (p < or = 0.005). Patients reported a well-being evaluation improvement about 66% in the group returning to work without restriction, 13% in those with limitation, 6% no further working; worse or unchanged well-being evaluation was found in 9% of patients returning to work without restriction, 3% with limitation, 3% no further working (p < or = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

Patients with thyroid diseases from areas of endemic goitre in Northern Italy were examined for thyroid antibodies by passive haemoagglutination. Of 40 schoolboys with goitre only one had thyroid antibodies (AT) in the blood. Among 182 adults with grade 1-2 goitre, examined within an area of low endemia, the frequency of AT was 7%, not significantly different from that found in the 286 persons with thyroid `O' living in the same area. Among 181 adults with grade 2-3 goitre, examined within an area of serious endemia, the frequency of AT was 16%; the percentage went up to 24% in 144 patients operated on for goitre. AT frequency was 36% in 87 patients with toxic goitre, more than 70% in 97 patients with Graves' disease and 17% in 60 patients with cancer of the thyroid. AT occurred three times more frequently in women than in men. Microsomal antibodies were more frequently detected than anti-thyroglobulin antibodies: the opposite was true in thyroid cancer. Lymphocytic infiltration (IL) of the gland was observed in 45% of the 464 simple goitres and in 52% of the 60 cancers of the thyroid: it was more frequent and intense in women. Among the 144 patients operated on for goitre the frequency and the titre of AT progressed in parallel with the intensity of the lymphocytic infiltration. Patients with a greater lymphocytic infiltration and higher AT had a higher TSH. Multinodular non-toxic goitre and autoimmune lymphocytic thyroiditis can be present in the same thyroid gland and the clinical expression will depend on which condition predominates. [ABSTRACT FROM AUTHOR]

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