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The flavonoid chrysin is an effective vascular Ca V 1.2 channel blocker. The aim of this study was to explore the chemical space around chrysin to identify the structural features that can be modified to develop novel and more effective blockers. Four derivatives (Chrysin 1-4) were synthesised and a functional, electrophysiology and molecular docking approach was pursued to assess their binding mode to Ca V 1.2 channels and their activity in vascular preparations. Methylation of the 5- and 7-OH of the chrysin backbone caused a marked reduction of the Ca 2+ antagonistic potency and efficacy. However, C-8 derivatives showed biophysical features similar to those of the parent compound and, like nicardipine, bound with high affinity to and stabilised the Ca V 1.2 channel in its inactivated state. The vasorelaxant effects of the four derivatives appeared vessel-specific, addressing the molecules' derivatization towards different targets. In conclusion, the scaffold of chrysin may be considered a valuable starting point for the development of innovative vascular Ca V 1.2 channel blockers., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Background: Duodenal neuroendocrine tumors (NETs) are uncommon, accounting for less than 4% of all gastrointestinal neoplasms. Prognosis is related to tumoral staging and grading, as well as to the specific subtype. In this article, we retrospectively describe the clinical presentation and surgical treatment of two rare large duodenal NETs: a high-grade G3 NET and a Gangliocytic Paraganglioma (GP)., Methods: Both patients presented with moderate-to-high-degree abdominal pain, without jaundice. Main vessel involvement and metastatic spread were excluded with imaging, while preoperative bioptic diagnosis was obtained via percutaneous needle citology and endoscopic ultrasound., Results: The presence of a sessile large lesion contraindicated any conservative approach in favor of a pancreaticoduodenectomy (PD). The detection of soft pancreatic tissue and a narrowed main pancreatic duct led us to perform a pancreaticogastrostomy to restore proper pancreatic drainage and to minimize the risk of postoperative leakage., Conclusion: PD may be a favorable choice in these cases; this procedure is challenging, but it results in a safer and more favorable clinical outcome for our patients. Pancreaticogastrostomy may guarantee lower rates of postoperative leak and appears to be preferred in this subset of patients.

Immunosuppressed patients can present with opportunistic infections resulting from an intrinsic systemic disease, which easily evolves into more aggressive and less common conditions. This work reports a clinical case of a female patient with histoplasmosis lesions in the nasal and oral mucosa, including pulmonary, hematological, and hepatic impairment, which led to the diagnosis of HIV seropositivity. In the presence of severe immunosuppression, morbidity is increased due to deep fungal infections and their unusual clinical characteristics can make diagnosis difficult. Therefore, it can be very helpful to recognize these clinical characteristics in order to determine early diagnostic interventions. It is important to recognize mucocutaneous manifestations of histoplasmosis because the biopsy of these lesions, and subsequent histopathological analysis, is one of the quickest, safest, and cheapest methods of diagnosis., (© 2024 Special Care Dentistry Association and Wiley Periodicals LLC.)

Papillary thyroid microcarcinoma (PTMC) represents 35-40% of all papillary cancers; it is defined as a nodule ≤ 10 mm at the time of histological diagnosis. The clinical significance of PTMC is still controversial, and it may be discovered in two settings: incidental PTMC (iPTMC), in which it is identified postoperatively upon histological examination of thyroid specimens following thyroid surgery for benign disease, and nonincidental PTMC (niPTMC), in which it is diagnosed before surgery. While iPTMC appears to be related to mild behavior and favorable clinical outcomes, niPTMC may exhibit markers of aggressiveness. We retrospectively review our experience, selecting 54 PTMCs: 28 classified as niPTMC (52%) and 26 classified as iPTMC (48%). Patients with niPTMC showed significant differences, such as younger age at diagnosis ( p < 0.001); a lower male/female ratio ( p < 0.01); a larger mean nodule diameter ( p < 0.001); and a higher rate of aggressive pathological findings, such as multifocality, capsular invasion and/or lymphovascular invasion ( p = 0.035). Other differences found in the niPTMC subgroup included a higher preoperative serum TSH level, higher hospital morbidity and a greater need for postoperative iodine ablation therapy ( p < 0.05), while disease-free long-term survival did not differ between subgroups ( p = 0.331) after a mean follow-up (FU) of 87 months, with one nodal recurrence among niPTMCs. The differences between iPTMC and niPTMC were consistent: patients operated on for total thyroidectomy and showing iPTMC can be considered healed after surgery, and follow-up should be designed to properly calibrate hormonal supplementation; conversely, niPTMC may sometimes exhibit aggressive behavior, and so the FU regimen should be closer and aimed at early detection of cancer recurrence.

Cinnamic acid and its derivatives represent attractive building blocks for the development of pharmacological tools. A series of piperoniloyl and cinnamoyl-based amides (6-9 a-f) have been synthesized and assayed against a wide panel of colorectal cancer (CRC) cells, with the aim of finding promising anticancer agents. Among all twenty-four synthesized molecules, 7a, 7e-f, 9c, and 9f displayed the best antiproliferative activity. The induced G1 cell cycle arrest and the increase in apoptotic cell death was seen in FACS analysis and western Blotting in the colon tumor cell lines HCT116, SW480, LoVo, and HT29, but not in the nontumor cell line HCEC. In particular, 9f overcame the resistance of HT29 cells, which have a mutant p53 and BRAF. Furthermore, 9f, amide of piperonilic acid with the 3,4-dichlorobenzyl substituent upregulated p21, which is involved in cell cycle arrest as well as in apoptosis induction. Cinnamic acid derivatives might be potential anticancer compounds, useful for the development of promising anti-CRC agents., (© 2023 The Authors. Chemical Biology & Drug Design published by John Wiley & Sons Ltd.)

Background and Objectives: MRI connectomics is an ideal tool to test a network-based model of pathologic propagation from a disease epicenter in neurodegenerative disorders. In this study, we used a novel graph theory-based MRI paradigm to explore functional connectivity reorganization, discerning between direct and indirect connections from disease epicenters, and its relationship with neurodegeneration across clinical presentations of the frontotemporal dementia (FTD) spectrum, including behavioral variant of FTD (bvFTD), nonfluent variant of primary progressive aphasia (nfvPPA), and semantic variant of primary progressive aphasia (svPPA)., Methods: In this observational cross-sectional study, disease epicenters were defined as the peaks of atrophy of a cohort of patients with high confidence of frontotemporal lobar degeneration pathology (Mayo Clinic). These were used as seed regions for stepwise functional connectivity (SFC) analyses in an independent (Milan) set of patients with FTD to assess connectivity in regions directly and indirectly connected to the epicenters. Correlations between SFC architecture in healthy conditions and atrophy patterns in patients with FTD were also tested., Results: As defined by comparing the 42 Mayo Clinic patients with 15 controls, disease epicenters were the left anterior insula for bvFTD, left supplementary motor area for nfvPPA, and left inferior temporal gyrus (ITG) for svPPA. Compared with 94 age-matched controls, patients with bvFTD (n = 64) and nfvPPA (n = 34) of the Milan cohort showed widespread decreased SFC in bilateral cortical regions with direct/indirect connections with epicenters and increased SFC either in directly connected regions, physically close to the respective seed region, or in more distant cortical/cerebellar areas with indirect connections. Across all link steps, svPPA (n = 36) showed SFC decrease mostly within the temporal lobes, with co-occurrent SFC increase in cerebellar regions at indirect link steps. The average stepwise topological distance from the left ITG in a reference group of 50 young healthy controls correlated with regional gray matter volume in svPPA, consistent with network-based degeneration., Discussion: Our findings demonstrate that each FTD syndrome is associated with a characteristic interplay of decreased and increased functional connectivity with the disease epicenter, affecting both direct and indirect connections. SFC revealed novel insights regarding the topology of functional disconnection across FTD syndromes, holding the promise to be used to model disease progression in future longitudinal studies., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Anastomotic leakage (AL) represents a major post-operative complication after low anterior resection (LAR) for rectal cancer. It is associated with increased morbidity, mortality, length of hospital stay and risk of permanent stoma. Herein we report the case of a 75-year-old male patient submitted to a minimally invasive LAR who developed an AL on the fifth post-operative day. This complication has been successfully managed by placing a Vacuum-Assisted Therapy device (Endo-SPONGE®) with an unusual Transanal Minimally Invasive Surgery (TAMIS) approach; the size of the abscess cavity was measured and the Endo-SPONGE® was cut according to the size of the fistulous defect. This procedure has been performed at regular intervals, achieving quick reduction of anastomotic defect. After the discharge from our department, the patient was addressed to adjuvant treatment. TAMIS may represent an alternative to the endoscopic approach to position an Endo-SPONGE® whenever a conservative management of an AL is required., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2023.)

Background and Aim: After the approval of the anti-Sars-CoV-2 vaccines for the pediatric population, it is necessary to encourage the immunization of children aged 5-11 years, as this can reduce intergenerational transmission. Therefore, this goal has become a priority for the COVID 19 vaccination campaign in Italy. In the city of Milan, the mass vaccination center (MVC) Fiera Milano City, previously settled for general population, became the main site to host pediatric vaccinations. The center was consequently remodeled to ensure a suitable space for children. This paper provides an overview on the organization strategy implemented by Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. The modular structure and the wide surface available in the center allowed the administration of hundreds of vaccines per day, especially in the first opening phase., Methods: All the data for the entire period of activity of Fiera MCV, from December 16th 2021 to February 20th 2022, were analyzed using descriptive statistics., Results: During the entire period of activity, from 16 December 2021 to 20 February 2022, 23% of the population in the province of Milan aged 5-11 years has been reached and vaccinated with at least one shot of vaccine in this center., Conclusions: Despite an enthusiastic response in the first weeks of the campaign, a progressive reduction in vaccination adherence was observed, maybe due to the absence of restrictive measures for unvaccinated children in Italy.

Morin is a vasorelaxant flavonoid, whose activity is ascribable to Ca V 1.2 channel blockade that, however, is weak as compared to that of clinically used therapeutic agents. A conventional strategy to circumvent this drawback is to synthesize new derivatives differently decorated and, in this context, morin-derivatives able to interact with Ca V 1.2 channels were found by employing the potential of PLATO in target fishing and reverse screening. Three different derivatives (5a-c) were selected as promising tools, synthesized, and investigated in in vitro functional studies using rat aorta rings and rat tail artery myocytes. 5a-c were found more effective vasorelaxant agents than the naturally occurring parent compound and antagonized both electro- and pharmaco-mechanical coupling in an endothelium-independent manner. 5a, the series' most potent, reduced also Ca 2+ mobilization from intracellular store sites. Furthermore, 5a≈5c > 5b inhibited Ba 2+ current through Ca V 1.2 channels. However, compound 5a caused also a concentration-dependent inhibition of K Ca 1.1 channel currents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In the field of pharmaceutical research, a branch that has become more and more interesting is phytochemistry. Among phytochemicals, flavonoids have been studied a lot over the past 30 years. This review summarizes the chemical characteristics, metabolism, applications, and toxicity of a particular flavonoid, chrysin, recorded in the last 10 years and supported by solid biological assays. Furthermore, this review highlights some derivatives of chrysin investigated to obtain more bioavailable molecules that maintain or improve chrysin's bioactivities, enclosing a chrysin patent section, as well., (© 2022 Deutsche Pharmazeutische Gesellschaft.)

Rapid and complete wound healing is a clinical emergency, mainly in pathological conditions such as Type 2 Diabetes mellitus. Many therapeutic tools are not resolutive, and the research for a more efficient remedial remains a challenge. Wound dressings play an essential role in diabetic wound healing. In particular, biocompatible hydrogels represent the most attractive wound dressings due to their ability to retain moisture as well as ability to act as a barrier against bacteria. In the last years, different functionalized hydrogels have been proposed as wound dressing materials, showing encouraging outcomes with great benefits in the healing of the diabetic wounds. Specifically, because of their excellent biocompatibility and biodegradability, natural bioactive compounds, as well as biomacromolecules such as polysaccharides and protein, are usually employed in the biomedical field. In this review, readers can find the main discoveries regarding the employment of naturally occurring compounds and biopolymers as wound healing promoters with antibacterial activity. The emerging approaches and engineered devices for effective wound care in diabetic patients are reported and deeply investigated.

Lung cancer has the highest cancer incidence, and it is the most common cause of cancer death worldwide. Cutaneous metastases are infrequent compared to hilar nodes, adrenal glands, liver, brain, and bones. However, unusual skin lesions in patients at high risk of lung cancer should be regarded carefully to rule out a metastatic manifestation of an occult primary site tumor. Surgical excision, or incisional biopsy when the former is deemed unfeasible, should be performed to allow histopathological examination in case of occult primary site. In patients affected by advanced lung tumors, surgical excision could be beneficial in terms of pain control and improvement of the quality of life. We report a case of a solitary large skin lesion as an early manifestation of a lung adenocarcinoma., Competing Interests: The authors have no conflicts of interest to declare., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Small bowel adenocarcinomas (SBA) are a rare entity associated with a poor prognosis and an advanced stage of disease at diagnosis. Surgical resection is considered the gold standard of treatment for stage I-III, while stage IV disease approach is still debated. We present a case of a young woman affected by a duodenojejunal junction SBA treated with surgical resection and FOLFOX adjuvant chemotherapy. The patient later underwent a palliative duodenojejunal bypass for peritoneal carcinomatosis., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2022.)

Background: Intestinal arteriovenous malformation is an abnormal connection between arteries and veins that bypasses the capillary system and may be a cause of significant lower gastrointestinal bleeding. On endoscopy, arteriovenous malformations are usually flat or elevated, bright red lesions. Overall, rectal localization of arteriovenous malformations is rare. The same may be said about polypoid shape arteriovenous malformations. Herein, we present a case of a large rectal polypoid arteriovenous malformations., Methods: Clinical, diagnostic, and treatment modalities of the patient were reviewed. Pre- and post-operative parameters were collected and analyzed. The clinical English literature is also reviewed and discussed., Results: A 60-year-old female patient was admitted to our emergency department for rectorrhagia and anemia. Rectoscopy revealed a polypoid lesion in the rectum and the biopsy showed fibrosis, necrosis areas, and hyperplastic glands. A total body contrast-enhanced computed tomography (CT) was performed revealing a parietal pseudonodular thickening with concentric growth and contrast enhancement, extending for about 53 mm. The mass wasn't removed endoscopically due to concentric growth, sessile implant, and submucosal nature. The patient underwent an uneventful laparoscopic anterior rectal resection. The postoperative hospitalization was free of complications. Histology showed the presence of a polypoid AVM composed of dilated arteries, veins, capillaries, and lymphatics, engaging the submucosa, muscularis, and subserosa layer., Conclusion: After a review of the current English literature, we found only one case of rectal polypoid AVM. The scarcity of documented cases encumbers optimal diagnostic and treatment approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Krizzuk, Cotesta, Galiffa, Peluso, Falbo, Biancucci, Puscio, Michelotto, Pasecinic, Montalto and Sammartino.)

Oxidative stress and endoplasmic reticulum stress (ERS) are strictly involved in myocardial ischemia/reperfusion (MI/R). Selenoprotein T (SELENOT), a vital thioredoxin-like selenoprotein, is crucial for ER homeostasis and cardiomyocyte differentiation and protection, likely acting as a redox-sensing protein during MI/R. Here, we designed a small peptide (PSELT), encompassing the redox site of SELENOT, and investigated whether its pre-conditioning cardioprotective effect resulted from modulating ERS during I/R. The Langendorff rat heart model was employed for hemodynamic analysis, while mechanistic studies were performed in perfused hearts and H9c2 cardiomyoblasts. PSELT improved the post-ischemic contractile recovery, reducing infarct size and LDH release with and without the ERS inducer tunicamycin (TM). Mechanistically, I/R and TM upregulated SELENOT expression, which was further enhanced by PSELT. PSELT also prevented the expression of the ERS markers CHOP and ATF6, reduced cardiac lipid peroxidation and protein oxidation, and increased SOD and catalase activities. An inert PSELT (I-PSELT) lacking selenocysteine was ineffective. In H9c2 cells, H 2 O 2 decreased cell viability and SELENOT expression, while PSELT rescued protein levels protecting against cell death. In SELENOT-deficient H9c2 cells, H 2 O 2 exacerbated cell death, that was partially mitigated by PSELT. Microscopy analysis revealed that a fluorescent form of PSELT was internalized into cardiomyocytes with a perinuclear distribution. Conclusions: The cell-permeable PSELT is able to induce pharmacological preconditioning cardioprotection by mitigating ERS and oxidative stress, and by regulating endogenous SELENOT.

Hemorrhagic Cholecystitis is a rare condition and usually represents a complication of acute cholecystitis. The clinical presentation is quite overlapping and usually involves abdominal pain that may be associated with fever, jaundice, nausea, vomiting, and finally haemobilia. It frequently involves patients with preexisting conditions such as chronic kidney disease undergoing hemodialysis or anticoagulation therapy. Due to the deadly potential of this condition attention must be high during diagnostics and treatment in order to avoid an ill-fated conclusion. To our knowledge, there is a lack of a comprehensive review on the subject as most of the literature consists of case reports or small case series. In order to give a contribution to improving the treatment strategy of this condition, we report a case successfully treated with cholecystectomy, and performed a literature review. Using the term "Hemorrhagic Cholecystitis", on PubMed database we found 67 cases reported in the English literature. The cases were analyzed by two researchers and clinical information was extrapolated and organized, aiming to create a comprehensive review on the subject, that may be clear and useful in clinical practice. KEY WORDS: Hemorrhagic cholecystitis, Surgical treatment.

Introduction: The aim of this study is to perform a review of the English-language international literature concerning thyroid surgery performed through the transoral vestibular approach, to evaluate its flessibility and safety in terms of complications., Materials and Method: The review was carried out on 17 studies of 17 different Authors. The following variables were taken into consideration: first Author's name, nationality, year of publication, number of cases, hospital stay, conversion rate, type of surgical approach, total number of total thyroidectomies and loboisthmectomies, operative time range, intraoperative blood loss range, number and percentage of complications., Results: 736 procedures were performed: 289 total thyroidectomies and 447 loboisthmectomies. Surgical approach was trivestibular in 15 cases and combined (oro-vestibular) in 2 cases. The operative time varies from 43 minutes for a loboisthmectomy to 345 for a total thyroidectomy. Intraoperative blood loss ranges from 3 to 300 ml. Ten cases were converted into open surgery. The hospital stay varies from 1 to 10 days. Complications were: transient recurrent laryngeal nerve palsy in 34 cases, permanent in 2 cases; transient hypoparathyroidism in 62 cases. One case of postoperative bleeding, 22 postoperative seroma, 20 cases of mental nerve injury, 8 cases of operative wound infection., Conclusions: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a new surgical method, the use of which exclusively meets the aesthetic needs of some patients. Its specific complication is the injury of the mental nerves. Further studies, however, seem to be necessary, on numerically broader cases, to ascertain the real validity of the method.

Aim: The aim of the present study is to report our series of incidental thyroid carcinomas in the last 15 years and their follow-up, discussing therapeutics indications and surgical choices., Patients and Methods: We have considered 1793 patients operated on Surgical Sciences Department of "Sapienza" University of Rome from January 1, 2001 to December 31, 2015. The study was conducted on 83 totally thyroidectomized patients with a real incidental thyroid carcinoma, by clinical, laboratory and instrumental controls. Whole-body scan was the most important test in postoperative evaluation., Results: In our series, the incidence of incidental carcinomas was 4.62%. Compared to the total number of cancer patients, the percentage is 21,9%. In 15.66% of cases there was multifocality and in 7.23% also bilaterality. Regarding the histological type, in all cases they were papillary carcinoma. The size of the neoplastic lesions ranged from a minimum of 3 to a maximum of 10 mm. Whole-body scan revealed lymph node metastasis in 57.69% of patients., Discussion: Comparing these data with our previous studies we have seen a significant increase in incidence of incidental thyroid carcinomas over the years. Our therapeutical choice is total thyroidectomy and complection thyroidectomy after lobectomy, because of a relevant percentage of multifocality and/or bilaterality of these tumors. Many Authors on the contrary prefer a more conservative approach invoking the good prognosis of these tumors. The 57.69% of lymph node metastasis at postoperative whole-body scan comfort us in our setting., Conclusion: Incidental thyroid carcinomas are not uncommon. We consider only tumors until 1 cm in diameter. Multifocality and bilaterality are often present such as occult lymph node metastasis. Our therapeutical choice is total thyroidectomy in order to conduct a proper follow-up.

Purpose: To investigate the use of metal oxide silicon field effect transistors (MOSFETs) as in vivo dosimetry detectors during electron beams at high dose-per-pulse intraoperative radiotherapy., Methods and Materials: The MOSFET system response in terms of reproducibility, energy, dose rate and temperature dependence, dose-linearity from 1 to 25 Gy, angular response, and dose perturbation was analyzed in the 6-9-MeV electron beam energy range produced by an intraoperative radiotherapy-dedicated mobile accelerator. We compared these with the 6- and 9-MeV electron beams produced by a conventional accelerator. MOSFETs were also used in clinical dosimetry., Results: In experimental conditions, the overall uncertainty of the MOSFET response was within 3.5% (+/-SD). The investigated electron energies and the dose rate did not significantly influence the MOSFET calibration factors. The dose perturbation was negligible. In vivo dosimetry results were in accordance with the predicted values within +/-5%. A discordance occurred either for an incorrect position of the dosimeter on the patient or when a great difference existed between the clinical and calibration setup, particularly when performing exit dose measurements., Conclusion: Metal oxide silicon field effect transistors are suitable for in vivo dosimetry during intraoperative radiotherapy because their overall uncertainty is comparable to the accuracy required in target dose delivery.