Columnar Mesomorphism in a Methylthio-Decorated Triindole for Enhanced Charge Transport.

We report a semiconducting triindole-based discotic liquid crystal (TRISMe) functionalized with six p-methylthiophenyl groups at its periphery. While initially a crystalline solid at room temperature, TRISMe transitions to a columnar hexagonal mesophase upon heating and retains this supramolecular organization upon subsequent cooling, despite having only three flexible alkyl chains attached to the core's nitrogens. The incorporation of methylthio groups effectively hinders tight molecular packing, stabilizing the columnar arrangement of this disk-shaped molecule. Single crystal analysis confirmed the high tendency of this compound to organize into a columnar architecture and the role played by the methylthio groups in reinforcing such structure. The mesomorphic behavior of TRISMe provides an opportunity for processing from its molten state. Notably, our research reveals significant differences in charge transport depending on the processing method, whether solution drop-casting or melt-based. TRISMe shows hole mobility values averaging 3 × 10-1 cm2 V-1 s-1 when incorporated in diode-type devices from the isotropic melt and annealed at the mesophase temperature, estimated by SCLC (space-charge-limited current) measurements. However, when integrated into solution-processed organic field-effect transistors (OFETs), crystalline TRISMe exhibits a hole mobility of 3 × 10-4 cm2 V-1 s-1. The observed differences can be attributed to a beneficial supramolecular assembly achieved in the mesophase in spite of its lower order. These results emphasize the material's potential for applications in easy-to-process electronic devices and highlight the potential of methylthio moieties in promoting columnar mesophases.

Improvement in Smell Using Monoclonal Antibodies Among Patients With Chronic Rhinosinusitis With Nasal Polyps: A Systematic Review.

BACKGROUND: Impairment of smell is more commonly related to chronic rhinosinusitis with nasal polyps (CRSwNP) than without, especially when asthma and/or NSAID-exacerbated respiratory disease and type 2 inflammation are also present. Therapeutic options include intranasal and systemic corticosteroids, surgery, and, more recently, biological therapy. We summarize current knowledge on the effect of biologics on olfaction in patients with CRSwNP. METHODS: We performed a systematic search of the PubMed and Cochrane databases from January 2001 to June 2022. The inclusion criteria were as follows: adult patients with CRS treated with dupilumab, omalizumab, mepolizumab, benralizumab, or reslizumab; and studies published in English reporting outcomes for sense of smell based on psychophysical and/or subjective tools. We excluded reports that did not assess CRSwNP, loss of smell evaluated with a method other than those accepted in the inclusion criteria, review articles, and expert opinions. No funding was received. RESULTS: Dupilumab has demonstrated rapid and sustained long-term improvement in smell in clinical trials and in real life. Omalizumab improves smell at 24 weeks. This improvement is maintained in the long-term, although it is not clinically relevant. Mepolizumab and benralizumab improved smell in the long term based on a subjective scale. No studies examining the improvement in smell in patients with CRSwNP treated with reslizumab were found. Indirect comparisons by meta-analysis consistently conclude that dupilumab is the most effective biologic for improving impaired sense of smell. CONCLUSION: Dupilumab seems to be more efficacious for improving the sense of smell than omalizumab, mepolizumab, and benralizumab.

Exacerbations Among Patients With Asthma Are Largely Dependent on the Presence of Multimorbidity.

BACKGROUND AND OBJECTIVE: Comorbidities can influence asthma control and promote asthma exacerbations (AEs). However, the impact of multimorbidity in AEs, assessed based on long-term follow-up of patients with asthma of different degrees of severity, has received little attention in real-life conditions. To describe the epidemiological and clinical characteristics and predictors of AEs in patients who had presented at least 1 AE in the previous year in the MEchanism of Genesis and Evolution of Asthma (MEGA) cohort. METHODS: The work-up included a detailed clinical examination, pulmonary function testing, fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick-tests, asthma questionnaires, and assessment of multimorbidity. The number of moderate-severe AEs in the preceding year was registered for each patient. RESULTS: The study population comprised 486 patients with asthma (23.7% mild, 35% moderate, 41.3% severe). Disease remained uncontrolled in 41.9%, and 47.3% presented ≥1 moderate-severe AE, with a mean (SD) annual exacerbation rate of 0.47 (0.91) vs 2.11 (2.82) in mild and severe asthma, respectively. Comorbidity was detected in 56.4% (66.6% among those with severe asthma). Bronchiectasis, chronic rhinosinusitis with nasal polyps, atopy, psychiatric illnesses, hyperlipidemia, and hypertension were significantly associated with AEs. No associations were found for FeNO, blood eosinophils, or total serum IgE. Sputum eosinophilia and a high-T2 inflammatory pattern were significantly associated with AEs. Multivariable regression analysis showed a significant association with asthma severity, uncontrolled disease, and low prebronchodilator FEV1/FVC. CONCLUSION: Our study revealed a high frequency of AE in the MEGA cohort. This was strongly associated with multimorbidity, asthma severity, poor asthma control, airflow obstruction, higher sputum eosinophils, and a very high-T2 inflammatory pattern.

Improvement in Olfaction in Patients With CRSwNP and Severe Asthma Taking Anti-IgE and Anti-IL-5 Biologics: A Real-Life Study.

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non-N-ERD subgroups. METHODS: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab). RESULTS: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. CONCLUSIONS: This is the first real-world study to compare improvement in olfaction among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non-N-ERD groups.

Muscular pseudotumor revealing a mycobacterial granuloma after bacillus Calmette-Guérin therapy.

INTRODUCTION: The Bacillus Calmette-Guérin (BCG) is a live attenuated strain of Mycobacterium bovis. Intravesical therapy with BCG has long been proved to be effective in treating early-stage bladder carcinoma. CASE REPORT: A 81-year-old male patient with former history of BCG instillations for bladder cancer two years ago was admitted in February 2020 to our department for a pulsatile and painful tumefaction of the right thigh that lasted for 6 months, due to a muscular M. bovis granuloma leading to femoral artery erosion. Emergency vascular surgery associated with prolonged antibiotherapy provided full recovery. DISCUSSION: Late infectious complications of intravesical BCG instillations are classical but rare. Isolated muscular involvement is exceptional. CONCLUSION: Mycobacterial infection should be carefully screened face to a granuloma presenting as muscular pseudotumor. A history of BCG therapy, even decades earlier, enhances this hypothesis and should lead to enforce microbiological testing, especially molecular test.

Study of the Addition Mechanism of 1H-Indazole and Its 4-, 5-, 6-, and 7-Nitro Derivatives to Formaldehyde in Aqueous Hydrochloric Acid Solutions.

The reaction of NH-indazoles with formaldehyde in aqueous hydrochloric acid has been experimentally studied by solution and solid-state nuclear magnetic resonance (NMR) and crystallography. The mechanism of the formation of N1-CH2OH derivatives was determined. For the first time, 2-substituted derivatives have been characterized by multinuclear NMR. Theoretically, calculations with gauge-invariant atomic orbitals (GIAOs) at the Becke three-parameter (exchange) Lee-Yang-Parr B3LYP/6-311++G(d,p) level have provided a sound basis for the experimental observations. The first X-ray structures of four (1H-indazol-1-yl)methanol derivatives are reported.

The Effect of Auxiliary Nitrogenated Linkers on the Design of New Cadmium-Based Coordination Polymers as Sensors for the Detection of Explosive Materials.

Three new cadmium-based coordination polymers, denoted [Cd(hfipbb)(4,4'-bipy)] (CdPF-1), [Cd(hfipbb)(2,2'-bipy)] (CdPF-2), and [Cd(hfipbb)(1,10-phen)] (CdPF-3), have been hydrothermally synthesized by using the well-known V-shaped organic linker 4,4'-(hexafluoroisopropylidene)bis(benzoic acid) (H2 hfipbb), together with different nitrogenated auxiliary linkers. Considering the d10 configuration of the transition metal selected, the luminescent properties for these CdPF-n materials were explored, finding that materials CdPF-2 and CdPF-3 act as excellent sensors in the detection of explosive nitro aromatic compounds. The photoluminescence properties of CdPF-2 and CdPF-3 revealed that significant and sensitive fluorescence quenching was observed toward NP (nitrophenol) for CdPF-2 and PA (picric acid) for CdPF-3 in MeOH suspensions.

Functional Examination of the Upper and Lower Airways in Asthma and Respiratory Allergic Diseases: Considerations in the Post-SARS-CoV-2 Era.

Airway examination procedures can potentially transmit infectious diseases to patients and to the health care professionals who perform them via various mechanisms. The COVID-19 pandemic has halted most of the activity of the clinics and laboratories involved in assessment of lung and nasal function, and clear recommendations in this regard have been made. Today, we still do not know for sure what its consequences will be in the short or long term, since important gaps remain in our knowledge of aspects as fundamental as virus transmission mechanisms, pathophysiology, immune response, and diagnosis. In this review, we study the examination techniques used to assess patients with respiratory allergy, asthma, and associated diseases during this period and highlight their possible advantages and disadvantages. Therefore, we focus on exploring the entire upper and lower airways, from the perspective of the safety of both health professionals and patients and their specific characteristics. We also analyze the intrinsic value of these interventions in terms of diagnosis and patient management. The changing situation of COVID-19 may mean that some of the assertions presented in this review will have to be modified in the future. While we seek to ensure a consistently broad approach, some differences in operational details may apply owing to local regulations.

Successful outcome following resection of metachronous pancreatic metastasis from a rhabdomyosarcoma.

BACKGROUND: Pancreatic metastases (PM) are rare, comprising 3% of pancreatic tumours removed in sizable series of operations. This report presents the first case of metachronous pancreatic metastases from rhabdomyosarcoma successfully treated by pancreaticoduodenectomy. CASE REPORT: A 19-year old man was admitted with a tumor in the head of the pancreas, 1 year after undergoing removal of an alveolar RMS from the right hand. . Computed tomography (CT) scan demonstrates a solitary hypodence tumour of the pancreas. The patient underwent a pancreaticoduodenectomy and the postoperative course was uneventful. Pathologic examination confirmed the metastatic alveolar RMS without lymph node involvement. At most recent follow-up, 36 months after pancreaticoduodenectomy, the patient has no evidence of disease. CONCLUSION: Although rare, rhabdomyosarcoma can metastasize to the pancreas. The surgeons must be aware of this complication, and that such pancreatic metastases are potentially resectable with a good long term outcome.

Actividad antifúngica del aceite volátil de Hedyosmum sp, frente a especies del género Candida / Antifungal activity of the volatile oil of Hedyosmum sp, Against species of the genus Candida

El objetivo del estudio fue determinar la actividad antifúngica del aceite volátil de las partes aéreas de la especie vegetal Hedyosmum sp., frente al complejo Candida albicans, C. glabrata, C. tropicalis y C. parapsilosis. El material vegetal se recolectó del bosque natural Jacarón, Provincia de Chimborazo, Ecuador. La extracción del aceite volátil se realizó por hidrodestilación, obteniéndose un rendimiento de 0,09%. La actividad antifúngica fue estudiada mediante el método de difusión en agar y los resultados se interpretaron mediante detección-medición de halos de inhibición y concentración mínima inhibitoria. El estudio se realizó partiendo del aceite puro y diluciones con dimetil sulfóxido. Los resultados se validaron mediante controles positivos (Fluconazol) y negativos (dimetil sulfóxido). El aceite puro mostró actividad antifúngica frente a C. albicans, C. tropicalis, C. parapsilosis, pero no frente a C. glabrata. Mientras que, la actividad antifúngica determinada empleando diluciones del aceite permitió establecer la concentración mínima inhibitoria para C. tropicalis, C. parapsilosis, en 0,25x106 µg/mL y para C. albicans en 0,5x106 µg/mL. Estos resultados concluyeron que el aceite volátil de Hedyosmum sp., presenta actividad antifúngica poco significativa frente a tres de las cuatro especies de Candida estudiadas

The objective of the study was to determine the antifungal activity of the volatile oil of the aerial parts of the plant species Hedyosmum sp., against Candida albicans, C. glabrata, C. tropicalis and C. parapsilosis complex. The plant material was collected from the Jacarón natural forest, Chimborazo Province, Ecuador. The extraction of the essential oil was carried out by hydro-distillation, obtaining a yield of 0.09%. Antifungal activity was studied by means of the diffusion in agar method and the results were interpreted by detection-measurement of inhibition halos and minimum inhibitory concentration. The study was carried out starting from the pure oil and dilutions with dimethyl sulfoxide. The results were validated by positive controls (Fluconazole) and negative controls (dimethyl sulfoxide). The pure oil showed antifungal activity against C. albicans, C. tropicalis, and C. parapsilosis complex, but not against C. glabrata. While, the antifungal activity determined using dilutions of the oil allowed establishing the minimum inhibitory concentration for C. tropicalis, C. parapsilosis complex, at 0,25x106 µg/mL and for C. albicans at 0,5x106 µg/mL. These results concluded that the volatile oil of Hedyosmum sp., Presents little antifungal activity against three of the four Candida species studied

Effect of anti-IgE in occupational asthma caused by exposure to low molecular weight agents.

BACKGROUND: The role of immunoglobulin (Ig)-E in occupational asthma (OA) due to low molecular weight (LMW) agents is not well established compared to classical atopic asthma. In this study, we evaluate whether anti-IgE monoclonal antibody (mAb) has an effect in a mouse model of OA, using persulfate salts. METHODS: On days 1 and 8, BALB/C mice were dermally sensitized with 5% ammonium persulfate (AP) or dimethyl sulfoxide (DMSO). On days 15, 18, and 21, animals were injected intraperitoneally with anti-IgE mAb or PBS 6 hours before challenge with AP or saline. Airway hyper-responsiveness (AHR) using a methacholine test, airway inflammation in bronchoalveolar lavage (BAL) and lung tissue, and total free IgE in serum samples were analyzed 24, 48, and 96 hours after the last challenge. RESULTS: Anti-IgE mAb treatment almost completely neutralized free serum IgE. In AP-sensitized and challenged mice, anti-IgE mAb treatment abolished AHR 24 hour and 48 hour after the last challenge and significantly reduced the total number of eosinophils and neutrophils 48 hour and 96 hour after the last AP challenge compared with nontreated mice. Levels of interleukin (IL)-13 in BAL were also significantly decreased after anti-IgE administration 24 hour and 48 hour after the last AP challenge. Histological analysis of the lung sections from anti-IgE-treated mice revealed normal inflammatory patterns similar to control groups 48 hour after the last challenge. CONCLUSIONS: Anti-IgE-treated mice showed a significant improvement in asthma features related to the AHR and airway inflammation. Anti-IgE mAb has positive effects in OA induced by persulfate salts.

Negligible effects of tryptophan on the aflatoxin adsorption of sodium bentonite.

The main objective of this study was to determine if the competitive adsorption of tryptophan (Trp) and aflatoxin B1 (AFB1) could potentially affect the ability of a sodium bentonite (NaB) to prevent aflatoxicosis in monogastric animals. The adsorption of Trp and AFB1 on this adsorbent is fast and could be operating on the same time-scale making competition feasible. In vitro competitive adsorption experiments under simulated gastrointestinal conditions were performed. A high affinity of the clay for Trp and NaB was observed. The effect of an excess of KCl to mimic the ionic strength of the physiological conditions were also investigated. A six-times decrease in the Trp surface excess at saturation was observed. A similar behaviour was previously found for AFB1 adsorption. Taking into account the amount of Trp adsorbed by the clay and the usual adsorbent supplementation level in diets, a decrease in Trp bioavailability is not expected to occur. Tryptophan adsorption isotherms on NaB were 'S'-shaped and were adjusted by the Frumkin-Fowler-Guggenheim model. The reversibility of the adsorption processes was investigated in order to check a potential decrease in the ability of NaB to protect birds against chronic aflatoxicoses. Adsorption processes were completely reversible for Trp, while almost irreversible for AFB1. In spite of the high affinity of the NaB for Trp, probably due to the reversible character of Trp adsorption, no changes in the AFB1 adsorption isotherm were observed when an excess of the amino acid was added to the adsorption medium. As a consequence of the preferential and irreversible AFB1 adsorption and the reversible weak binding of Trp to the NaB, no changes in the aflatoxin sorption ability of the clay are expected to occur in the gastrointestinal tract of birds.

ETV5 cooperates with LPP as a sensor of extracellular signals and promotes EMT in endometrial carcinomas.

Endometrial carcinoma (EC) is the most frequent among infiltrating tumors of the female genital tract, with myometrial invasion representing an increase in the rate of recurrences and a decrease in survival. We have previously described ETV5 transcription factor associated with myometrial infiltration in human ECs. In this work, we further investigated ETV5 orchestrating downstream effects to confer the tumor the invasive capabilities needed to disseminate in the early stages of EC dissemination. Molecular profiling evidenced ETV5 having a direct role on epithelial-to-mesenchymal transition (EMT). In particular, ETV5 modulated Zeb1 expression and E-Cadherin repression leading to a complete reorganization of cell-cell and cell-substrate contacts. ETV5-promoted EMT resulted in the acquisition of migratory and invasive capabilities in endometrial cell lines. Furthermore, we identified the lipoma-preferred partner protein as a regulatory partner of ETV5, acting as a sensor for extracellular signals promoting tumor invasion. All together, we propose ETV5-transcriptional regulation of the EMT process through a crosstalk with the tumor surrounding microenvironment, as a principal event initiating EC invasion.

Sarcoidosis and the kidney: not only the granulomatous interstitial nephritis.

Renal involvement in sarcoidosis displays a wide range of manifestations, and kidney dysfunction may involve all three mechanisms of renal failure. We report a new case of systemic sarcoidosis presenting as a severe renal failure due to hypercalcemia, sarcoidosis-related bilateral nephrolithiasis and granulomatous interstitial nephritis. A prostate adenocarcinoma was also diagnosed, but has to be regarded as an unrelated disease.

Novel molecular profiles of endometrial cancer-new light through old windows.

Endometrial carcinoma (EC) is the most common gynecological malignancy in the western world. A widely accepted dualistic model, which has been established on a morphological basis, differentiates EC into two broad categories: Type I oestrogen-dependent adenocarcinoma with an endometrioid morphology and Type II non-oestrogen-dependent EC with a serous papillary or clear cell morphology. Molecular genetic evidence indicates that endometrial carcinoma, as described in other malignancies, likely develops as the result of a stepwise accumulation of alterations in cellular regulatory pathways, such as oncogene activation and tumor suppressor gene inactivation, which lead to dysfunctional cell growth. These molecular alterations appear to be specific in Type I and Type II cancers. In type I endometrioid endometrial cancer, PTEN gene silencing in conjunction with defects in DNA mismatch repair genes, as evidenced by the microsatellite instability phenotype, or mutations in the K-ras and/or beta-catenin genes, are recognized major alterations, which define the progression of the normal endometrium to hyperplasia, to endometrial intraepithelial neoplasia, and then on to carcinoma. In contrast, Type II cancers show mutations of TP53 and Her-2/neu and seem to arise from a background of atrophic endometrium. Nevertheless, despite the great effort made to establish a molecularly-based histological classification, the following issues must still be clarified: what triggers the tumor cells to invade the myometrium and what causes vascular or lymphatic dissemination, finally culminating in metastasis? RUNX1, a transcription factor, was recently identified as one of the most highly over-expressed genes in a microarray study of invasive endometrial carcinoma. Another candidate gene, which may be associated with an initial switch to myometrial infiltration, is the transcription factor ETV5/ERM. These studies, as well as those conducted for other genes possibly involved in the mitotic checkpoint as a major mechanism of carcinogenesis in non-endometrioid endometrial cancer, could help in understanding the differences in the biology and the clinical outcome among histological types.

Hostility and helper T-cells in patients with bulimia nervosa.

OBJECTIVE: The study aimed to analyze the correlation between lymphocyte counts and several psychopathological variables associated with psychological instability (depression, hostility, impulsivity, self-defeating personality traits, and borderline personality symptoms) in patients with bulimia nervosa (BN). METHOD: Sixty BN patients were assessed, using specific scales for eating pathology, general psychopathology, impulsivity, depression, and borderline personality features. Lymphocyte and lymphocyte subset counts were performed. Plasma cortisol at 8:00, before and after administration of 1 mg of dexamethasone at 23:00, was determined. The influence of body weight, and the use of tobacco, alcohol, and caffeine was controlled. The relationship between each isolated variable and the number of immune cells was analyzed. In a second step, supplementary post-hoc analysis of the variables was introduced to confirm the accuracy of the psychopathological assessment. RESULTS: Hostility was negatively correlated with the number of helper T-cells (CD4+). Patients with high hostility had lower CD4+ cell counts and lower CD4+/CD8+ ratios. In the post-hoc control study, hostility was significantly related with other "interpersonal" items. CONCLUSIONS: These results support the idea that hostility, as an expression of disturbed interpersonal relationships, could play a role as a modulator of immune activity in patients with BN.