Radiology of fibrosis. Part I: Thoracic organs.

Sustained injury from factors such as hypoxia, infection, or physical damage may provoke improper tissue repair and the anomalous deposition of connective tissue that causes fibrosis. This phenomenon may take place in any organ, ultimately leading to their dysfunction and eventual failure. Tissue fibrosis has also been found to be central in both the process of carcinogenesis and cancer progression. Thus, its prompt diagnosis and regular monitoring is necessary for implementing effective disease-modifying interventions aiming to reduce mortality and improve overall quality of life. While significant research has been conducted on these subjects, a comprehensive understanding of how their relationship manifests through modern imaging techniques remains to be established. This work intends to provide a comprehensive overview of imaging technologies relevant to the detection of fibrosis affecting thoracic organs as well as to explore potential future advancements in this field.

Radiology of fibrosis part II: abdominal organs.

Fibrosis is the aberrant process of connective tissue deposition from abnormal tissue repair in response to sustained tissue injury caused by hypoxia, infection, or physical damage. It can affect almost all organs in the body causing dysfunction and ultimate organ failure. Tissue fibrosis also plays a vital role in carcinogenesis and cancer progression. The early and accurate diagnosis of organ fibrosis along with adequate surveillance are helpful to implement early disease-modifying interventions, important to reduce mortality and improve quality of life. While extensive research has already been carried out on the topic, a thorough understanding of how this relationship reveals itself using modern imaging techniques has yet to be established. This work outlines the ways in which fibrosis shows up in abdominal organs and has listed the most relevant imaging technologies employed for its detection. New imaging technologies and developments are discussed along with their promising applications in the early detection of organ fibrosis.

Radiology of fibrosis part III: genitourinary system.

Fibrosis is a pathological process involving the abnormal deposition of connective tissue, resulting from improper tissue repair in response to sustained injury caused by hypoxia, infection, or physical damage. It can impact any organ, leading to their dysfunction and eventual failure. Additionally, tissue fibrosis plays an important role in carcinogenesis and the progression of cancer.Early and accurate diagnosis of organ fibrosis, coupled with regular surveillance, is essential for timely disease-modifying interventions, ultimately reducing mortality and enhancing quality of life. While extensive research has already been carried out on the topics of aberrant wound healing and fibrogenesis, we lack a thorough understanding of how their relationship reveals itself through modern imaging techniques.This paper focuses on fibrosis of the genito-urinary system, detailing relevant imaging technologies used for its detection and exploring future directions.

Genetic screening for hereditary transthyretin amyloidosis with polyneuropathy in western Sicily: Two years of experience in a neurological clinic.

BACKGROUND AND PURPOSE: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate generating amyloid fibrils. METHODS: A prospective systematic genetic screening for ATTRv-PN was proposed in patients presenting with a sensory-motor idiopathic polyneuropathy and two or more "red flags" among the following: family history of polyneuropathy or cardiopathy, bilateral carpal tunnel syndrome, cardiac insufficiency, renal amyloidosis, lumbar tract stenosis, autonomic dysfunction, idiopathic gastrointestinal disease, amyloid deposits on biopsy, and vitreous opacities. The detection rate was calculated, and nonparametric analyses were carried out to underline differences among screened positive versus negative patients. RESULTS: In the first step, 145 suspected patients underwent genetic testing, revealing a diagnosis of ATTRv-PN in 14 patients (10%). Then, cascade screening allowed early recognition of 33 additional individuals (seven symptomatic ATTRv-PN patients and 26 presymptomatic carriers) among 84 first-degree relatives. Patients with a positive genetic test presented a higher frequency of unexplained weight loss, gastrointestinal symptoms, and family history of cardiopathy. CONCLUSIONS: A systematic screening for ATTRv-PN yielded an increased recognition of the disease in our neurological clinic. Unexplained weight loss associated with axonal polyneuropathy had the highest predictive value in the guidance of clinical suspicion. A focused approach for the screening of ATTRv-PN could lead to an earlier diagnosis and identification of asymptomatic carriers, who will be promptly treated after a strict follow-up at the clinical onset.

Mechanisms linking bariatric surgery to adipose tissue, glucose metabolism, fatty liver disease and gut microbiota.

PURPOSE: In the last 20 years, bariatric surgery has achieved an important role in translational and clinical research because of obesity comorbidities. Initially, a tool to lose weight, bariatric surgery now has been shown to be involved in several metabolic pathways. METHODS: We conducted a narrative review discussing the underlying mechanisms that could explain the impact of bariatric surgery and the relationship between obesity and adipose tissue, T2D, gut microbiota, and NAFLD. RESULTS: Bariatric surgery has an impact in the relation between obesity and type 2 diabetes, but in addition  it induces the white-to-brown adipocyte trans-differentiation, by enhancing thermogenesis. Another issue is the connection of bariatric surgery with the gut microbiota and its role in the complex mechanism underlying weight gain. CONCLUSION: Bariatric surgery modifies gut microbiota, and these modifications influence lipid metabolism, leading to improvement of non-alcoholic fatty liver disease.

Microbiome Dysbiosis: A Pathological Mechanism at the Intersection of Obesity and Glaucoma.

The rate at which obesity is becoming an epidemic in many countries is alarming. Obese individuals have a high risk of developing elevated intraocular pressure and glaucoma. Additionally, glaucoma is a disease of epidemic proportions. It is characterized by neurodegeneration and neuroinflammation with optic neuropathy and the death of retinal ganglion cells (RGC). On the other hand, there is growing interest in microbiome dysbiosis, particularly in the gut, which has been widely acknowledged to play a prominent role in the etiology of metabolic illnesses such as obesity. Recently, studies have begun to highlight the fact that microbiome dysbiosis could play a critical role in the onset and progression of several neurodegenerative diseases, as well as in the development and progression of several ocular disorders. In obese individuals, gut microbiome dysbiosis can induce endotoxemia and systemic inflammation by causing intestinal barrier malfunction. As a result, bacteria and their metabolites could be delivered via the bloodstream or mesenteric lymphatic vessels to ocular regions at the level of the retina and optic nerve, causing tissue degeneration and neuroinflammation. Nowadays, there is preliminary evidence for the existence of brain and intraocular microbiomes. The altered microbiome of the gut could perturb the resident brain-ocular microbiome ecosystem which, in turn, could exacerbate the local inflammation. All these processes, finally, could lead to the death of RGC and neurodegeneration. The purpose of this literature review is to explore the recent evidence on the role of gut microbiome dysbiosis and related inflammation as common mechanisms underlying obesity and glaucoma.

Cytotoxicity of quercetin is related to mitochondrial respiration impairment in Saccharomyces cerevisiae.

Quercetin is a flavonol ubiquitously present in fruits and vegetables that shows a potential therapeutic use in non-transmissible chronic diseases, such as cancer and diabetes. Although this phytochemical has shown promising health benefits, the molecular mechanism behind this compound is still unclear. Interestingly, quercetin displays toxic properties against phylogenetically distant organisms such as bacteria and eukaryotic cells, suggesting that its molecular target resides on a highly conserved pathway. The cytotoxicity of quercetin could be explained by energy depletion occasioned by mitochondrial respiration impairment and its concomitant pleiotropic effect. Thereby, the molecular basis of quercetin cytotoxicity could shed light on potential molecular mechanisms associated with its health benefits. Nonetheless, the evidence supporting this hypothesis is still lacking. Thus, this study aimed to evaluate whether quercetin supplementation affects mitochondrial respiration and whether this is related to quercetin cytotoxicity. Saccharomyces cerevisiae was used as a study model to assess the effect of quercetin on energetic metabolism. Herein, we provide evidence that quercetin supplementation: (1) decreased the exponential growth of S. cerevisiae in a glucose-dependent manner; (2) affected diauxic growth in a similar way to antimycin A (complex III inhibitor of electron transport chain); (3) suppressed the growth of S. cerevisiae cultures supplemented with non-fermentable carbon sources (glycerol and lactate); (4) promoted a glucose-dependent inhibition of the basal, maximal, and ATP-linked respiration; (5) diminished complex II and IV activities. Altogether, these data indicate that quercetin disturbs mitochondrial respiration between the ubiquinone pool and cytochrome c, and this phenotype is associated with its cytotoxic properties.

Cellulolytic bacteria joined with deproteinized whey decrease carbon to nitrogen ratio and improve stability of compost from wine production chain by-products.

Composting residues from wine and dairy chains would contribute to increase the environmental sustainability of the production. The aim of this study was to evaluate the effects of deproteinized whey combined with bioactivators on the composting process. Bacillus velezensis and Kocuria rhizophila, bacteria with cellulolytic activity, were isolated from raw materials and inoculated in the organic mass to be composted. Piles moistened with deproteinized whey showed the highest reduction of total and dissolved organic carbon due to the stimulation of bacterial activity by nitrogen compounds held within deproteinized whey. Such findings were also confirmed by the speed up of the microbial carbon mineralization. Bioactivators and deproteinized whey speeded up the composting process and returned compost characterized by high stability and quality. The addition of available N is crucial to improve the composting process and can act even better if combined with cellulolytic bacteria.

Cytoplasmic localization of the cell polarity factor scribble supports liver tumor formation and tumor cell invasiveness.

The loss of epithelial cell polarity plays an important role in the development and progression of liver cancer. However, the specific molecular mechanisms supporting tumor initiation and progression are poorly understood. In this study, transcriptome data and immunofluorescence stains of tissue samples derived from hepatocellular carcinoma (HCC) patients revealed that overexpression associated with cytoplasmic localization of the basolateral cell polarity complex protein scribble (Scrib) correlated with poor prognosis of HCC patients. In comparison with HCC cells stably expressing wild-type Scrib (ScribWT ), mutated Scrib with enforced cytoplasmic enrichment (ScribP305L ) induced AKT signaling through the destabilization of phosphatase and tensin homolog (PTEN) and PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1). Cytoplasmic ScribP305L stimulated a gene signature and a phenotype characteristic for epithelial to mesenchymal transition (EMT) and HCC cell invasiveness. ScribP305L -dependent invasion was mediated by the activator protein 1 (AP-1) constituents ATF2 and JunB through induction of paracrine-acting secreted protein acidic and cysteine-rich (SPARC). Coexpression of ScribP305L and the oncogene c-MYC through hydrodynamic gene delivery in mouse livers promoted tumor formation and increased abundance of pAKT, pATF2, and SPARC in comparison with controls. Finally, cytoplasmic Scrib localization correlated with AKT and ATF2 phosphorylation in human HCC tissues, and the ScribP305L -dependent gene signature was enriched in cancer patients with poor prognosis. CONCLUSION: Perturbation of hepatocellular polarity due to overexpression and cytoplasmic enrichment of Scrib supports tumor initiation and HCC cell dissemination through specific molecular mechanisms. Biomarker signatures identified in this study can be used for the identification of HCC patients with higher risk for the development of metastasis. (Hepatology 2018;67:1842-1856).

Production of a Mixture of Fengycins with Surfactant and Antifungal Activities by Bacillus sp. MA04, a Versatile PGPR.

Bacillus sp. strain MA04 a plant growth-promoting rhizobacteria (PGPR) showed hemolytic activity on blood agar plates, and the supernatant from liquid culture in nutrient broth at 24 h exhibited emulsification activity, suggesting the production of biosurfactants. In antagonist assays, the supernatant showed antifungal activity against phytopathogenic fungi such as Penicillium expansum, Fusarium stilboides, Sclerotium rolfsii y Rhizoctonia solani, finding a reduction of mycelial growth of all fungi tested, ranging from 35 to 69%, this activity was increased with time of culture, accomplishing percentages of inhibition up to 85% with supernatants obtained at 72 h. Then, the crude biorsurfactant (CB) was isolated from the supernatant in order to assay its antagonistic effect on the phytopathogens previously tested, finding an increase in the inhibition up to 97% at 500 mg/L of CB. The composition of CB was determined by infrared spectroscopy, identifying various functional groups related to lipopeptides, which were purified by high-performance liquid chromatography and analyzed by MALDI-TOF/TOF-MS, revealing a mixture of fengycins A and B whose high antifungal activity is been widely recognized. These results show that PGPR Bacillus sp. MA04 could also contribute to plant health status through the production of metabolites with antimicrobial activity.

Post-COVID-19 Unilateral Upper Lip Numbness: A Case Report.

This is a case of a 63-year-old female with post-COVID-19 unilateral upper lip pain and numbness. Neurologic examination did not reveal any deficits other than deficits on pinprick in the maxillary division (V2) of the left trigeminal nerve. Brain neuroimaging showed signs of acute inflammation of the left maxillary sinus. Neuropraxia of the infraorbital nerve, a branch of the trigeminal nerve, was the diagnosis considered. Reports on trigeminal neurosensory changes following acute sinusitis are few, and isolated trigeminal neuropathy is rare except in cases of dental disorders. Up to this writing, there have been no reports on post-COVID-19 unilateral upper lip numbness and pain. This study will also serve as a concise review on the correlative neuroanatomy of the trigeminal nerve.

Exploring public interest in gut microbiome dysbiosis, NAFLD, and probiotics using Google Trends.

Scientific interest related to the role of gut microbiome dysbiosis in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) has now been established and is constantly growing. Therefore, balancing dysbiosis, through probiotics, would be a potential therapy. In addition to scientific interest, on the other hand, it is important to evaluate the interest in these topics among the population. This study aimed to analyze, temporally and geographically, the public's interest in gut microbiome dysbiosis, NAFLD, and the use of gut probiotics. The most widely used free tool for analyzing online behavior is Google Trends. Using Google Trends data, we have analyzed worldwide volume searches for the terms "gut microbiome", "dysbiosis", "NAFLD" and "gut probiotic" for the period from 1, January 2007 to 31 December 2022. Google's relative search volume (RSV) was collected for all terms and analyzed temporally and geographically. The RSV for the term "gut microbiome" has a growth rate of more than 1400% followed, by "gut probiotics" (829%), NAFLD (795%), and "dysbiosis" (267%) from 2007 to 2012. In Australia and New Zealand, we found the highest RSV score for the term "dysbiosis" and "gut probiotics". Moreover, we found the highest RSV score for the term "NAFLD" in the three countries: South Korea, Singapore, and the Philippines. Google Trends analysis showed that people all over the world are interested in and aware of gut microbiome dysbiosis, NAFLD, and the use of gut probiotics. These data change over time and have a geographical distribution that could reflect the epidemiological worldwide condition of NAFLD and the state of the probiotic market.

Prognostic Impact of Atrial Fibrillation Pattern and other Clinical Biomarkers in Patients with Stroke Admitted in a Tertiary Hospital in Cebu City from 2015-2022.

Background: The effect of atrial fibrillation (AF) patterns and clinical biomarkers among patients with AF-related stroke is still controversial. Objectives: The objective of this study is to determine the association of the pattern of AF and markers on routine blood tests with the outcome of patients after an AF-related stroke. Methods: This is a retrospective cohort study of patients with stroke and AF admitted in a tertiary hospital in Cebu City from 2015-2022. Patients' baseline characteristics, laboratory tests, ECG, and radiologic data were collected. Descriptive statistics such as mean and frequency were computed. The Kaplan-Meier method and the log-rank test were used to calculate the incidence time. The Cox regression analysis was used to determine factors associated with survival. A stepwise regression technique was used in model building. Results: The mortality rate of patients with AF-related stroke was 0.02. A Kaplan Meier survival estimate shows that patients with paroxysmal AF have better survival. Upon model building of variables, age, red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), platelet count, low density lipid cholesterol (LDL-C), and pattern of AF were predictive of mortality in patients with AF-related stroke. Conclusions: Among AF-related stroke patients admitted at a tertiary hospital in Cebu City, pattern of AF, age, RDW, NLR, platelet count, and LDL-C were associated with mortality. The parameters associated with increased mortality could be easily assessed using an ECG, CBC, and lipid profile. These are all readily available and cost-efficient.

Predictors for Hemorrhagic Transformation among Patients with Ischemic Stroke Admitted in a Tertiary Hospital in the Philippines from July 2018-July 2019.

Background: Among the multiple scoring systems for hemorrhagic transformation, only few of these address spontaneous hemorrhagic transformation after an ischemic stroke, with most done with Western population data. Objectives: This study aims to identify the predictors for hemorrhagic transformation among patients with ischemic stroke admitted in a tertiary hospital in Cebu City, Philippines. Methods: This is a retrospective cohort study of patients with ischemic stroke admitted in a tertiary hospital in Cebu City. Patients' baseline characteristics, clinical, and radiologic data were collected. Chi square test and t-test were used to determine which variables were significantly different between patients with and without hemorrhagic transformation. Odds ratio (OR) and 95% confidence interval (CI) were determined to measure the association between the different variables and hemorrhagic transformation. Results: A total of 500 ischemic stroke patients were included in the study. There were 28 (6%) ischemic stroke patients with Hemorrhagic Transformation. The mean age of these patients is 66.93 ± 12.42 years, 48.8% male, 10.8% had atrial fibrillation, and 2.4% had myocardial infarction. Controlling for the effect of confounders, white blood cell count (OR 1.11; 95% CI 1.03-1.19), myocardial infarction (OR 5.25; 95% CI 1.13-24.34), and presence of brain edema (OR 2.86; 95% CI 1.05-7.80) were significant predictors of hemorrhagic transformation. Conclusion: White blood cell count, presence of brain edema, and myocardial infarction were significantly associated with hemorrhagic transformation among ischemic stroke patients.

Phosphorus recovery from ultrafiltered membrane wastewater by biochar adsorption columns: The effect of loading rates.

The present study used bench scale columns filled with biochar for phosphorous (P) recovery from real ultrafiltered wastewater. No studies are available about the potentiality of biochar using ultrafiltered real wastewater. Therefore, this study aimed to assess phosphate (PO4 3-) recovery by biochar-packed columns employing real treated wastewater from an ultrafiltration process. Three flow rates were tested, specifically 0.7, 1.7 and 2.3 L h-1, to gain insights into the optimal working conditions. Results revealed that the maximum amount of PO4 3- recovery (namely, 3.43 mg g-1 biochar) can be achieved after 7 h by employing the highest tested flow rate. Furthermore, the phosphorus exchange capacity (PEC) was inversely correlated with the feeding flow rate (FFR), with PEC values equal to 35, 25 and 9 % for FFR of 0.67, 1.7 and 2.3 L h-1, respectively. The pseudo-first order model best approximated the adsorption kinetics, thus suggesting that the adsorption of phosphate by biochar depends on its concentrations (i.e. physiosorption mechanism).

Transduodenal robotic ampullectomy: tips and tricks and strategies for postoperative duodenal fistula management (with video).

Transduodenal Ampullectomy (TA) is a procedure for resecting low-malignancy ampullary tumors, with postoperative fistula as a notable complication. This study aims to clarify the indications for TA, outline the surgical robotic technique, and emphasize the importance of comprehensive complication management alongside the surgical approach. This multimedia article provides a detailed exposition of the robotic TA surgical technique, including the most important steps involved in exposing and reimplanting biliary and pancreatic ducts. The procedure encompasses the mobilization of the hepatic flexure of the colon, an extensive Kocher maneuver for duodenal mobilization, and ampulla exposure through a duodenal incision. Employing retraction loop sutures enhances surgical field visibility. Reconstruction involves securing pancreatic and biliary ducts to the duodenal mucosa, each tutored with a silicon catheter, and suturing for ampullectomy completion. The total operative time was 380 min. Final histopathology disclosed high-grade dysplasia with an isolated focus of adenocarcinoma (pT1), accompanied by clear resection margins. A postoperative duodenal fistula occurred, managed successfully through conservative treatment, utilizing subcutaneous drainage. Despite accurate robotic TA execution, complications may arise. This study underscores the importance of a comprehensive approach, incorporating meticulous surgical technique and effective complication management, to optimize patient outcomes.

Percutaneous radiofrequency ablation of ovarian cancer metastasis in the spleen: a therapeutic option to consider.

Splenic metastasis are rare clinical entities developing in less than 1% of all metastatic cancers and usually in the setting of disseminated disease. To date, splenectomy is traditionally the first line therapy in patient with splenic metastasis, however non-surgical therapies have been reported. Here we described the case of a 57-year-old patient with splenic metastasis from ovarian cancer successfully treated by percutaneous radiofrequency ablation. Furthermore, we performed a literature systematic review of the cases of splenic metastases treated by thermal ablation.

Bilateral pheochromocytomas: clinical presentation and morbidity rate related to surgery technique and genetic status.

Background: Pheochromocytomas (PHEOs) are rare catecholamine-secreting adrenal tumors. Approximately 60-90% of bilateral PHEOs are hereditary. We retrospectively analyzed the clinical characteristics of patients with bilateral PHEOs and the morbidity rate (malignancy, tumor recurrence and adrenal insufficiency (AI) rate) related to surgery technique and genetic status of the patients. Results: Fourteen patients (12.5%, nine women, five men) had synchronous or metachronous bilateral PHEOs (out of 112 PHEO patients who underwent surgery between 1976 and 2021). The median age at diagnosis was 32 years (9-76) (three were children). Nine patients (64.2%) presented synchronous bilateral tumors, five (35.7%) contralateral metachronous tumors, 2-12 years after the first surgical intervention; three (21.4%) were metastatic. Median follow-up: 5 years (1-41), IQR 19 months. A total of 78.5% had a germline mutation (eight RET gene with MEN2A syndrome, three VHL syndrome, three not tested). Post-surgery recurrence was noted in 16.6% of patients (one with MEN2A syndrome and metastatic PHEOs, one with VHL syndrome), with similar rates after total adrenalectomy or cortical-sparing adrenal surgery. AI was avoided in 40% after cortical-sparing surgery. Conclusion: Bilateral PHEOs are usually associated with genetic syndromes. The surgical technique for patients with hereditary bilateral PHEOs should be chosen based on a personalized approach, as they are at higher risk for developing new adrenal tumors requiring additional surgeries.