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Abstract Background To evaluate and compare the long-term clinical and radiological outcomes of post-extraction sockets after ridge preservation either with porcine xenograft or collagen alone. Patients underwent single-tooth extraction in the posterior mandible. Fresh extraction sockets were filled with pre-hydrated cortico-cancellous porcine bone or collagen sponge. Two or 3 months later, a ridge expansion technique with immediate implant positioning placement was performed. Primary (alveolar width changes) and secondary outcomes (adverse events and long-term maintenance of buccal plate covering the implant) were evaluated. Results Thirty-four women and 20 men were selected: 30 implants (group A) placed into healed post-extraction sockets grafted with porcine bone and 24 (group B) into sockets filled with a collagen sponge. There was a significant loss in width in both groups from the first and second surgery (ranging between 2.7 mm and 4.5 mm). The ridge splitting with bone expansion resulted in significant long-term increases in width for both procedures and implant sites. Non-significant differences in alveolar width were registered between the groups at 10-year follow-up even if the analysis of the implant buccal bone coverage suggested that group A had significantly worst results. Conclusions Porcine bone group had significantly better short-term outcomes with lower long-term maintenance of the buccal plate.

Peliosis hepatis (PH) is a rare benign pathological entity characterised by dilatation of the hepatic sinusoids. It has been reported to be associated with infection or malignancy, but the aetiology of PH remains unknown. Distinguishing PH from other malignancies can be difficult on imaging studies. This case report describes the incidental finding of PH in a patient undergoing a cardiac computed tomography (CT) scan at our institution.The CT scan incidentally revealed areas of altered density in the liver on the abdominal scans, requiring detailed liver diagnostic studies for better characterisation.

In an era of evolving literacy challenges, an Italian based project 'Leggere: Forte!' (Reading Strong) is promoting shared reading aloud to spark youth interest in reading and improve language skills. Now in its third year, the project team have analysed the impact of daily shared reading on 1829 children aged 3-10. The results show significant benefits in language, comprehension, and literacy, and highlight disparities between the experimental and the control groups. Teacher feedback underscores the positive effects of this version of shared reading. The initiative demonstrates the educational value of shared reading and calls for its integration into modern education, suggesting it as a foundation for further research and the development of rich, diverse learning environments.

Background: Intraductal papillary neoplasms of the bile duct (IPNB) are rare precancerous lesions with implications for the development of cholangiocarcinoma (CCA). Recognizing IPNB and managing its recurrence pose challenges in clinical practice. We present two cases. Case 1: a 60-year-old man presented with an 8 × 8 × 9 cm hepatic cyst initially suspected to be a hydatid cyst. Histology post-resection revealed an IPNB with foci of adenocarcinoma. Despite negative oncologic margins, recurrence occurred eight years later as an rT2N0 lesion. Surgical resection was performed without adjuvant chemotherapy, resulting in the patient’s survival at 48 months post-surgery. Case 2: a 28-year-old female with cognitive impairment was admitted with pulmonary embolism and a liver lesion diagnosed as a simple cyst. Subsequent evaluation revealed adenocarcinoma with local metastases, extensive vascular involvement, and thrombosis. Despite aggressive management, including thrombectomy and chemotherapy, the patient’s condition deteriorated, leading to hepatic failure and eventual demise. Conclusion: IPNB represents a rare premalignant subtype with a propensity for progression to CCA. R0 surgical resection typically offers favorable oncological outcomes with a minimal recurrence risk. Surgical intervention for localized resectable recurrence is both safe and feasible. International registries tracking IPNB recurrence are essential for advancing understanding and optimizing diagnosis, management, and treatment strategies.

Growing evidence suggests that opioid analgesics modulate angiogenesis during pathophysiological processes. Vascular endothelial growth factor-A (VEGF-A) was recently proposed to be involved in pain development. To date, no anti-angiogenic drug is used for pain management. When administered in a bioavailable formulation, (i.e., ultramicronized) N-palmitoylethanolamine (PEA) delays the onset of morphine tolerance, improves morphine analgesic activity and reduces angiogenesis in in vivo models. This study aimed at investigating whether VEGF-A is involved in PEA-induced delay of morphine tolerance. The anti-VEGF-A monoclonal antibody bevacizumab was used as a reference drug. Preemptive and concomitant treatment with ultramicronized PEA delayed morphine tolerance and potentiated the analgesic effect of morphine, while counteracting morphine-induced increase of VEGF-A in the nervous system. Similar results were obtained when bevacizumab was administered together with morphine. Of note, bevacizumab showed an analgesic effect per se. In equianalgesic treatment regimens (obtained through increasing morphine doses and associating PEA), PEA resulted in lower expression of VEGF-A in dorsal root ganglia (DRG) and spinal cord compared to morphine alone. Similar results were observed for plasma levels of the soluble VEGF receptor 1 (sFLT-1). Moreover, in morphine-treated animals, two pain-related genes (i.e., Serpina3n and Eaat2) showed a more than 3-fold increase in their expression at spinal cord and DRG level, with the increase being significantly counteracted by PEA treatment. This study supports the hypothesis that the effects of PEA on morphine analgesia and tolerance may be mediated by the down-modulation of VEGF-A and sFLT-1 in the nervous system and plasma, respectively.

In the field of surgery, the idea of performing organ transplants in a minimally invasive fashion has always been a significant technical challenge. The advent of the robotic approach facilitated the overcoming of difficulties in highly complex surgical procedures that demand high technical skill. Furthermore, robotic transplants are showing significant benefits in patient outcomes, particularly in the obese population. The purpose of this review is to provide an overview of the current state of robotics applications for transplant surgery. Kidney transplants were the first to be performed using a fully robotic approach. Since then, robotic surgery has gradually been applied to other organ transplants, with very recent reports of fully robotic lung and liver transplants. Further experiences and studies will be needed to verify their effectiveness and to satisfy some concerns regarding the longer warm ischemia time related to the robotic approach in comparison with open surgery.

Questo articolo si inserisce nel filone di studi che ripensano la questione della moneta attraverso una prospettiva multidisciplinare, riconosciuta come fondamentale per comprendere le sperimentazioni monetarie contemporanee e, in effetti, la natura stessa della moneta. Collegandoci alla proposta di Gómez e Dini (2016), utilizziamo i dati ottenuti da uno studio empirico su un caso situato in Argentina per contribuire alla ricerca sull’origine e sul significato della moneta. Attraverso l’analisi dei Chipicos, emessi da una cooperativa argentina, questo lavoro esplora le dinamiche sociali ed economiche emergenti, considerando anche le interconnessioni tra circolazione monetaria e riproduzione sociale. Inoltre, si indaga la questione sociologica dell’ontologia monetaria in relazione ai valori e alla moneta. L’analisi rivela come le monete alternative possano influenzare le relazioni sociali e offrire una prospettiva critica sulle teorie monetarie esistenti, arricchendo il dibattito accademico con contributi da filosofia, antropologia e sociologia.

IntroductionThis study comprehensively compared laparoscopic liver resection (LLR) to open liver resection (OLR) in treating colorectal cancer liver metastasis (CRLM).MethodsA systematic review of relevant literature was conducted to assess a range of crucial surgical and oncological outcomes.ResultsFindings indicate that minimally invasive surgery (MIS) did not significantly prolong the duration of surgery compared to open liver resection and notably demonstrated lower blood transfusion rates and reduced intraoperative blood loss. While some studies favored MIS for its lower complication rates, others did not establish a statistically significant difference. One study identified a lower post-operative mortality rate in the MIS group. Furthermore, MIS consistently correlated with shorter hospital stays, indicative of expedited post-operative recovery. Concerning oncological outcomes, while certain meta-analyses reported a lower rate of cancer recurrence in the MIS group, others found no significant disparity. Overall survival and disease-free survival remained comparable between the MIS and open liver resection groups.ConclusionThe analysis emphasizes the potential advantages of LLR in terms of surgical outcomes and aligns with existing literature findings in this field.Systematic review registration[website], identifier [registration number].

Reading involves both cognitive and psychological activities of combining both pre-existing cultural and linguistic knowledge. The reader has the ability to view the world in the light of his/her own cultural experiences which are constructed consciously or unconsciously, and may seem to be fruitful in text analysis and exploring the uncovered multi layers of meanings. In relation to multifaceted cross-cultural environment and experiences, people world view undergoes a dynamic change due to their distinct norms, values, attributed to specific objects. The purpose of the study focuses on to collect feedback from the EFL learners on culturally nativizatized literary poem, ''I wandered Lonely as a Cloud'' by William Wordsworth, analyzed and discussed during reading process. This study aims to explain how EFL learners with distinct cultural schemata read and interpret a western culturally loaded texts differently. It also attempts to indicate how visual images, setting and figurative language of the nativized text may contribute to their interpretation and reading comprehension level. As a result, in reading nativized version and non-nativized version, they indicated similarities and differences in their responses and interpretations in these culturally overloaded discourses. The respondents, in this study, reflected different images and structures through nativization. In this qualitative study, the data was collected and analyzed by comparing familiar and unfamiliar contents of two distinct versions in the form of the learners' feedback through semi-structured interviews and questionnaires. The study asks for further investigation to look into the effect of cultural specific concepts on cross-cultural literary texts.

Background. In high-income countries, shopping for non-prescription multivitamin–multimineral supplements has tremendously increased. Objective and Methods. The purpose of this labeling analysis is to inform on the daily elemental iron (with or without vitamin C) supply provided by multivitamin–multimineral supplements sold online by Amazon in Western and Southern Europe (amazon.es®, amazon.de®, amazon.it®, and amazon.fr®). Results. We identified 298 iron-containing multivitamin–multimineral preparations sold by Amazon marketplaces: 153 preparations sourced from amazon.de®, 68 from amazon.fr®, 54 from amazon.it®, and 23 from amazon.es®. The daily iron dose provided by these preparations was 14 [5–14] mg (median and interquartile range), with no differences among the marketplaces. Approximately 90% (n = 265) of the preparations contained ferrous iron. Moreover, 85% (n = 253) of the preparations were fortified with vitamin C in a dose of 80 [40–100] mg daily. Conclusions. The median supply of iron (about 14 mg) and vitamin C (80 mg) in iron-containing multivitamin–multimineral preparations offered on Amazon platforms in Western and Southern Europe falls below that currently recommended for iron deficiency in review articles, namely 100 mg of iron and 500 mg of vitamin C per day. The iron supply of iron-containing multivitamin–multimineral preparations falls also below the dose of 30–60 mg advocated to prevent iron deficiency in menstruating women.

The potential of game-based experiential workshops to complement focus groups in identifying drivers/barriers to environmentally sustainable food systems was explored. Sixty adults from an Italian bio-district answered to a questionnaire; among them, nineteen and twenty-one people participated in a game-based experiential workshop and in a focus group, respectively. The experiential workshop involved games, image theater, and on-the-spot feedback. The body language recorded during the workshop captured information on the transparency of producers and on the oppression from public institutions as perceived by citizens. Experiential workshops may have advantages over focus groups in terms of diagnostic potential.

The purpose of this mixed-method research was to assess the attitudes and perceptions of a sample of 21 University level Saudi Undergraduate EFL students at Majma University, Community College towards using Padlet as a collaborative web-based online digital tool in reading classroom. Participants were enrolled in reading introductory course. The research applied by the researcher was basically descriptive in nature and survey method for which students’ oriented set of questionnaire was designed. The questionnaire included 21 items related with respondents’ different categories of variable constructs on 5points likert scale. The research tools used for data collection were semi-structured interviews, researcher’s observation and a questionnaire. Data collected revealed that respondents indicated positive attitudes towards Padlet application in reading classroom. Maximum number of students enjoyed Padlet tool with great zeal. Furthermore, students valued the instructors’ feedback and peer discussion using Padlet.

Removable functional appliances (RFA) have long been employed to address Class II malocclusion, particularly in cases involving a significant overjet, a deep bite, and molar class 2 issues. Notably divergent from RFA, myofunctional appliances (PMA) offer several distinct advantages, including applicability in noncompliant patients, adaptability in cases of dental element scarcity, suitability for allergic patients, impression-free utilization, and reduced costs. Within the array of clinical cases treated with PMA, we chose to present an intricate case involving an 8-year-old girl. Our aim was to showcase the immediate effects of PMA and to track the progress over a two-year span. Following one year of PMA treatment, substantial improvements were observed in a large overjet, a deep bite, and lip incompetence—factors often associated with elevated risks of dental trauma. These improvements not only positively impacted dental aesthetics but also engendered normalized nasal respiration and diminished palatal impingement, thereby enhancing the overall quality of life. Upon reaching the two-year mark, the clinical status pertaining to Class II malocclusion remained stable. Further treatment was advised in a subsequent phase to refine imperfections in the dental arch form. Nonetheless, comprehensive data from the prolonged follow-up of patients treated with these appliances are essential to establish robust scientific evidence concerning their long-term efficacy.

This study aimed to compare neuromuscular fatigability of the elbow flexors and extensors between athletes with amputation (AMP) and athletes with spinal cord injury (SCI) for maximum voluntary force (MVF) and rate of force development (RFD). We recruited 20 para-athletes among those participating at two training camps (2022) for Italian Paralympic veterans. Ten athletes with SCI (two with tetraplegia and eight with paraplegia) were compared to 10 athletes with amputation (above the knee, N = 3; below the knee, N = 6; forearm, N = 1). We quantified MVF, RFD at 50, 100, and 150 ms, and maximal RFD (RFDpeak) of elbow flexors and extensors before and after an incremental arm cranking to voluntary fatigue. We also measured the RFD scaling factor (RFD-SF), which is the linear relationship between peak force and peak RFD quantified in a series of ballistic contractions of submaximal amplitude. SCI showed lower levels of MVF and RFD in both muscle groups (all p values ≤ 0.045). Despite this, the decrease in MVF (Cohen’s d = 0.425, p < 0.001) and RFDpeak (d = 0.424, p = 0.003) after the incremental test did not show any difference between pathological conditions. Overall, RFD at 50 ms showed the greatest decrease (d = 0.741, p < 0.001), RFD at 100 ms showed a small decrease (d = 0.382, p = 0.020), and RFD at 150 ms did not decrease (p = 0.272). The RFD-SF decreased more in SCI than AMP (p < 0.0001). Muscle fatigability impacted not only maximal force expressions but also the quickness of ballistic contractions of submaximal amplitude, particularly in SCI. This may affect various sports and daily living activities of wheelchair users. Early RFD (i.e., ≤50 ms) was notably affected by muscle fatigability.

Brazilian journals play an important role in the local scientific scene. Despite its importance, Brazilian scientific production in Physics and Science education needs further articulation regarding the profile and impact of manuscripts. Therefore, our main goal in this paper is to monitor the trends in the Brazilian journals from 2013 to 2019 using scientometric tools. We analysed 3557 papers from 13 Brazilian electronic journals focused on science education and/or physics education, through impact and bibliometric metrics. The journals clustered into four very different groups regarding impact, and the individual time path could be drawn. In addition, an asymmetry could be identified in Brazilian publications, given the concentration of papers in "RBEF."

BackgroundInternational and national registries consistently report substantial differences in kidney transplant (KT) activity despite demonstrable clinical and financial benefits. The study aims to estimate the financial resources gained by KT and produce a benchmark analysis that would inform adequate strategies for the growth of the service.MethodsWe analyzed the KT activity in our region between 2017 and 2019. The benchmark analysis was conducted with programs identified from national and international registries. The estimate of financial resources was obtained by applying the kidney transplant coefficient of value; subsequently, we compared the different activity levels and savings generated by the three KT programs.FindingsThe KT activity in the region progressively declined in the study years, producing a parallel reduction of the estimated savings. Such savings were substantially inferior when compared to those generated by benchmark programs (range €18–22 million less).InterpretationThe factors influencing the reduced KT activity in the study period with the related “foregone savings” are multiple, as well as interdependent. Organ donation, access to the transplant waiting list, and KT from living donors appear to be the most prominent determinants of the observed different levels of activities. International experience suggests that a comprehensive strategy in the form of a “task force” may successfully address the critical areas of the service reversing the observed trend. The financial impact of a progressively reduced KT activity may be as critical as its clinical implications, jeopardizing the actual sustainability of services for patients with end-stage kidney disease.

To mineralize their shells, molluscs secrete a complex cocktail of proteins—collectively defined as the calcifying shell matrix—that remains occluded in the exoskeleton. Nowadays, protein extracts from shells are recognized as a potential source of bioactive substances, among which signalling molecules, bactericides or protease inhibitors offer the most tangible perspectives in applied sciences, health, and aquaculture. However, one technical obstacle in testing the activity of shell extracts lies in their high insolubility. In this paper, we present a protocol that circumvents this impediment. After an adapted shell protein extraction and the production of two organic fractions—one soluble, one insoluble—we employ a hand-operated tablet press machine to generate well-calibrated tablets composed of 100% insoluble shell matrix. FT-IR monitoring of the quality of the tablets shows that the pressure used in the press machine does not impair the molecular properties of the insoluble extracts. The produced tablets can be directly tested in different biological assays, such as the bactericidal inhibition zone assay in Petri dish, as illustrated here. Diverting the use of the hand-operated tablet press opens new perspectives in the analysis of insoluble shell matrices, for discovering novel bioactive components.

Human (h) carbonic anhydrase (CAs, EC 4.2.1.1) isoforms IX and XII were recently confirmed as anticancer targets against solid hypoxic tumours. The “three-tails approach” has been proposed as an extension of the forerunner “tail” and “dual-tail approach” to fully exploit the amino acid differences at the medium/outer active site rims among different hCAs and to obtain more isoform-selective inhibitors. Many three-tailed inhibitors (TTIs) showed higher selectivity against the tumour-associated isoforms hCA IX and XII with respect to the off-targets hCA I and II. X-ray crystallography studies were performed to investigate the binding mode of four TTIs in complex with a hCA IX mimic. The ability of the most potent and selective TTIs to reduce in vitro the viability of colon cancer (HT29), prostate adenocarcinoma (PC3), and breast cancer (ZR75-1) cell lines was evaluated in normoxic (21% O2) and hypoxic (3% O2) conditions demonstrating relevant anti-proliferative effects.

BACKGROUND: Epstein-Barr virus (EBV), also known as human herpesvirus 4, is one of the most common pathogenic viruses in humans. EBV mononucleosis always involves the spleen and as such it predisposes to splenic rupture, often without a trauma, and splenic infarction. Nowadays the goal of management is to preserve the spleen, thereby eliminating the risk of post-splenectomy infections. METHODS: To characterise these complications and their management, we performed a systematic review (PROSPERO CRD42022370268) following PRISMA guidelines in three databases: Excerpta Medica, the United States National Library of Medicine, and Web of Science. Articles listed in Google Scholar were also considered. Eligible articles were those describing splenic rupture or infarction in subjects with Epstein-Barr virus mononucleosis. RESULTS: In the literature, we found 171 articles published since 1970, documenting 186 cases with splenic rupture and 29 with infarction. Both conditions predominantly occurred in males, 60% and 70% respectively. Splenic rupture was preceded by a trauma in 17 (9.1%) cases. Approximately 80% (n = 139) of cases occurred within three weeks of the onset of mononucleosis symptoms. A correlation was found between the World Society of Emergency Surgery splenic rupture score, which was retrospectively calculated, and surgical management: splenectomy in 84% (n = 44) of cases with a severe score and in 58% (n = 70) of cases with a moderate or minor score (p = 0.001). The mortality rate of splenic rupture was 4.8% (n = 9). In splenic infarction, an underlying haematological condition was observed in 21% (n = 6) of cases. The treatment of splenic infarction was always conservative without any fatal outcomes. CONCLUSIONS: Similarly to traumatic splenic rupture, splenic preservation is increasingly common in the management of mononucleosis-associated cases as well. This complication is still occasionally fatal. Splenic infarction often occurs in subjects with a pre-existing haematological condition.

Primary hyperaldosteronism (PA) is one of the most common causes of secondary hypertension. PA may be associated with a decline in renal function. About 20% of cases with resistant HTN eventually cause PA, so all these patients should be evaluated for PA. Herein, we present a case with drug-resistant hypertension and chronic kidney disease (CKD), the cause of which was PA. Despite his low-salt diet modifications and treatment with several classes of antihypertensive medication, he had poorly controlled blood pressure (BP). Measurements of aldosterone and renin raised the concern of PA. Imaging confirmed bilateral adrenal hyperplasia. Due to the persistently high BP, despite the modification of the antihypertensive treatment, the patient underwent unilateral adrenalectomy, as the only feasible possibility of lowering aldosterone levels. After surgery, the patient had an improvement in both BP values and renal function. PA is difficult to diagnose in patients with CKD and Arterial Hypertension because hypertension is often associated with CKD, but PA accounts for a significant percentage of drug-resistant hypertension, so these patients should be screened for secondary arterial hypertension.

Background and Objectives: Underpowered immune response to vaccines against SARS-CoV-2 was observed in solid organ transplant (SOT) recipients. A novel combination of monoclonal antibodies tixagevimab-cilgavimab (TGM/CGM) received authorization as pre-exposure prophylaxis (PrEP) in those with reduced response to vaccine. We aimed to evaluate the response rate to COVID-19 vaccination in kidney transplant (KT), compared to liver transplant (LT) recipients, and the efficacy and safety of PrEP with TGM/CGM. Material and Methods: Between March and November 2022, adult KT and LT recipients who had completed the vaccination schedule (3 doses) were tested for anti-SARS-CoV-2 antibodies titer. SOT recipients with anti-SARS-CoV-2 titer ≥ 100 IU/mL were considered protected against infection, while those with titer < 100 UI/mL were defined non-protected. Patients with inadequate response were invited to PrEP. Results: In total, 306 patients were enrolled [KT:197 (64.4%), LT:109 (35.6%)]. After the complete scheme of vaccination, 246 (80.3%) patients developed a protective titer, while 60 (19.6%) did not have a protective titer. KT recipients had a lower rate of protective anti-COVID-19 titer compared to LT patients [149 (75.6%) vs. 97 (89.0%), p = 0.004]. Recipients with non-protective anti-COVID-19 titer received mainly tacrolimus-based regimen associated with mycophenolate mofetil (MMF) (70%) e steroids (46.7%) as maintenance immunosuppression, while those treated with everolimus were associated with higher protective titer. Of 35 (58.3%) patients who received PrEP, within 12 months, 6 (17.1%) (all KT) developed pauci-symptomatic COVID-19 disease, while 15/25 (60%) of non-responders, who did not receive the prophylaxis, developed COVID-19 disease. After PrEP, hospitalization rate was lower (2.8% vs. 16%), and no adverse events, neither graft loss nor rejection, were observed. Conclusions: Despite complete COVID-19 vaccination, SOT recipients might be not protected from the SARS-CoV-2 infection, especially after KT. In non-protected SOT patients, the subsequent pre-exposure prophylaxis with combination of monoclonal antibodies (TGM/CGM) might be an efficacy and safe strategy to prevent COVID-19 severe disease and hospitalization.

Highlights With improved management of patients, sepsis survivors are increasing each year. Early cardiovascular complications, of yet undeciphered mechanisms, are an emerging health issue in post-sepsis syndrome. Premature senescence of endothelium and vascular tissue is proven an accelerated process of atherogenesis in young septic rats. An increasing body of clinical evidence point at endothelial senescence in the initiation and development of atherosclerosis. Prevention of premature senescence by senotherapy and cardiological follow-up could improve long-term septic patients’ outcomes.

Experimental evidence suggests that neuroinflammation is a key pathological event of many diseases affecting the nervous system. It has been well recognized that these devastating illnesses (e.g., Alzheimer’s, Parkinson’s, depression, and chronic pain) are multifactorial, involving many pathogenic mechanisms, reason why pharmacological treatments are unsatisfactory. The purpose of this study was to evaluate the efficacy of a vegetal mixture capable of offering a multiple approach required to manage the multifactoriality of neuroinflammation. A mixture composed of Zingiber officinale (150 mg kg−1), Echinacea purpurea (20 mg kg−1), and Centella asiatica (200 mg kg−1) was tested in a mouse model of systemic neuroinflammation induced by lipopolysaccharide (LPS, 1 mg kg−1). Repeated treatment with the vegetal mixture was able to completely counteract thermal and mechanical allodynia as reported by the Cold plate and von Frey tests, respectively, and to reduce the motor impairments as demonstrated by the Rota rod test. Moreover, the mixture was capable of neutralizing the memory loss in the Passive avoidance test and reducing depressive-like behavior in the Porsolt test, while no efficacy was shown in decreasing anhedonia as demonstrated by the Sucrose preference test. Finally, LPS stimulation caused a significant increase in the activation of glial cells, of the central complement proteins and of inflammatory cytokines in selected regions of the central nervous system (CNS), which were rebalanced in animals treated with the vegetal mixture. In conclusion, the vegetal mixture tested thwarted the plethora of symptoms evoked by LPS, thus being a potential candidate for future investigations in the context of neuroinflammation.

ABSTRACT With progress in genome sequencing and data sharing, 1,000s of bacterial genomes are publicly available. Genome mining—using bioinformatics tools in terms of biosynthetic gene cluster (BGC) identification, analysis, and rating—has become a key technology to explore the capabilities for natural product (NP) biosynthesis. Comprehensively, analyzing the genetic potential of the phylum Bacteroidetes revealed Chitinophaga as the most talented genus in terms of BGC abundance and diversity. Guided by the computational predictions, we conducted a metabolomics and bioactivity driven NP discovery program on 25 Chitinophaga strains. High numbers of strain-specific metabolite buckets confirmed the upfront predicted biosynthetic potential and revealed a tremendous uncharted chemical space. Mining this data set, we isolated the new iron chelating nonribosomally synthesized cyclic tetradeca- and pentadecalipodepsipeptide antibiotics chitinopeptins with activity against Candida, produced by C. eiseniae DSM 22224 and C. flava KCTC 62435, respectively. IMPORTANCE The development of pipelines for anti-infectives to be applied in plant, animal, and human health management are dried up. However, the resistance development against compounds in use calls for new lead structures. To fill this gap and to enhance the probability of success for the discovery of new bioactive natural products, microbial taxa currently underinvestigated must be mined. This study investigates the potential within the bacterial phylum Bacteroidetes. A combination of omics-technologies revealed taxonomical hot spots for specialized metabolites. Genome- and metabolome-based analyses showed that the phylum covers a new chemical space compared with classic natural product producers. Members of the Bacteroidetes may thus present a promising bioresource for future screening and isolation campaigns.

The distinction between glial painful and protective pathways is unclear and the possibility to finely modulate the system is lacking. Focusing on painful neuropathies, we studied the role of interleukin 1α (IL-1α), an alarmin belonging to the larger family of damage-associated molecular patterns endogenously secreted to restore homeostasis.The treatment of rat primary neurons with increasing doses of the neurotoxic anticancer drug oxaliplatin (0.3–100μM, 48 h) induced the release of IL-1α. The knockdown of the alarmin in neurons leads to their higher mortality when co-cultured with astrocytes. This toxicity was related to increased extracellular ATP and decreased release of transforming growth factor β1, mostly produced by astrocytes.In a rat model of neuropathy induced by oxaliplatin, the intrathecal treatment with IL-1α was able to reduce mechanical and thermal hypersensitivity both after acute injection (100 ng and 300 ng) and continuous infusion (100 and 300 ng/die−1). Ex vivo analysis on spinal purified astrocyte processes (gliosomes) and nerve terminals (synaptosomes) revealed the property of IL-1α to reduce the endogenous glutamate release induced by oxaliplatin. This protective effect paralleled with an increased number of GFAP-positive cells in the spinal cord, suggesting the ability of IL-1α to evoke a positive, conservative astrocyte phenotype.Endogenous IL-1α induced protective signals in the cross-talk between neurons and astrocytes. Exogenously administered in rats, IL-1α prevented neuropathic pain in the presence of spinal glutamate decrease and astrocyte activation.

The term tendinopathy indicates a wide spectrum of conditions characterized by alterations in tendon tissue homeostatic response and damage to the extracellular matrix. The current pharmacological approach involves the use of nonsteroidal anti-inflammatory drugs and corticosteroids often with unsatisfactory results, making essential the identification of new treatments. In this study, the pro-regenerative and protective effects of an aqueous fibroin solution (0.5–500 μg/mL) against glucose oxidase (GOx)-induced damage in rat tenocytes were investigated. Then, fibroin anti-hyperalgesic and protective actions were evaluated in two models of tendinopathy induced in rats by collagenase or carrageenan injection, respectively. In vitro, 5–10 μg/mL fibroin per se increased cell viability and reverted the morphological alterations caused by GOx (0.1 U/mL). Fibroin 10 μg/mL evoked proliferative signaling upregulating the expression of decorin, scleraxin, tenomodulin (p

Minangkabau is a territory situated in West Sumatra Indonesia. The history of Minangkabau comes from an oral tradition which is then written and known as "Tambo". Many oral stories that appear in Minangkabau contain human values, for example the story of Malin Kundang which gives human values to be obedient to parents. Through this research, oral stories were collected from informants and written in the form of illustrated books. This study specifically collects children oral stories of Minangkabau, then analyzed, and made into a illustrated story book, because it is feared that these oral stories would disappear along with the death of the informants. These stories are written in the Minang language so that the young generation and children will keep maintaining and understanding the Minang language in daily life. Through the creative industry, oral stories are packaged into illustrated story books in Minang language. The benefit is that Minang children who live in Minang or beyond its areas will hopefully understand and can use the Minang language properly. The approach used in this research is the folklore approach by collecting stories spoken in the Minangkabau community that have not been written yet.

Abstract Background The Sudden Unexpected Infant Death Syndrome (SUID) is one of the leading causes of mortality in the first year of life. The aim of this work was the retrospective evaluation of the incidence of SUID and the effectiveness of the multiagency approach to this phenomenon in the Tuscany Region. Methods Data were obtained from the regional registry of SUID cases in the period 2009–2019. The registry contains both sudden unexpected deaths in the first week of life (Sudden Unexpected Early Neonatal Deaths - SUEND), and those occurring after the first week up to 1 year of age (SUID). Results In this timeframe a total of 73 sudden unexpected deaths occurred in our region; 32 were Unexplained (i.e. Sudden Infant Death Syndrome - SIDS), 24 Explained, 10 Undetermined, and 7 SUEND. Autopsies were performed in 91% of cases, and in 95% of these by three groups of selected pathologists according to our protocol. We found a low incidence of SUID (0.21 ‰), and SIDS deaths accounted for 0.1‰ of live births (48% of cases) with a high prevalence of infants of non-Italian ethnicity (38% of cases). Bereaved families were able to receive psychological support from mental health professionals and have contact with the family association, Seeds for SIDS. Audits were organized when post-mortem examinations were not carried out or carried out incorrectly in procedural terms, and when the diagnosis was particularly uncertain. Conclusions This paper first provides data on SUID mortality based on complete post-mortems in an Italian region. According to these findings we can state that our approach is effective both in terms of correctly performed autopsies and support for bereaved families. Future efforts are necessary to further reduce the incidence of SUID especially among non- Italian infants. An improvement action is also recommended for ensuring a more accurate and consistent picture of the circumstances of death. The final approval of the National Protocol for the management of SUID cases is therefore strongly advocated in order to improve surveillance in this specific field and abolish disparities among the Italian regions.