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One of the most exciting advances in life science research is the development of 3D cell culture systems to obtain complex structures called organoids and spheroids. These 3D cultures closely mimic in vivo conditions, where cells can grow and interact with their surroundings. This allows us to better study the spatio-temporal dynamics of organogenesis and organ function. Furthermore, physiologically relevant organoids cultures can be used for basic research, medical research, and drug discovery. Although most of the research thus far focuses on the development of heart, liver, kidney, and brain organoids, to name a few, most recently, these structures were obtained using dental stem cells to study in vitro tooth regeneration. This review aims to present the most up-to-date research showing how dental stem cells can be grown on specific biomaterials to induce their differentiation in 3D. The possibility of combining engineering and biology principles to replicate and/or increase tissue function has been an emerging and exciting field in medicine. The use of this methodology in dentistry has already yielded many interesting results paving the way for the improvement of dental care and successful therapies.

Non-communicable diseases (NCDs), including coronary heart disease, stroke, hypertension, type 2 diabetes, dementia, depression and cancers, are on the rise worldwide and are often associated with a lack of physical activity (PA). Globally, the levels of PA among individuals are below WHO recommendations. A lack of PA can increase morbidity and mortality, worsen the quality of life and increase the economic burden on individuals and society. In response to this trend, numerous organisations came together under one umbrella in Hamburg, Germany, in April 2021 and signed the ‘Hamburg Declaration’. This represented an international commitment to take all necessary actions to increase PA and improve the health of individuals to entire communities. Individuals and organisations are working together as the ‘Global Alliance for the Promotion of Physical Activity’ to drive long-term individual and population-wide behaviour change by collaborating with all stakeholders in the community: active hospitals, physical activity specialists, community services and healthcare providers, all achieving sustainable health goals for their patients/clients. The ‘Hamburg Declaration’ calls on national and international policymakers to take concrete action to promote daily PA and exercise at a population level and in healthcare settings.

The growth and persistence of alfalfa (Medicago sativa), a perennial legume capable of producing high yields of high-quality forage, is reduced in moderately acidic soils. The low performance of alfalfa at low pH is due to numerous factors that affect the host plant, their rhizobia, and the symbiotic interaction. Sinorhizobium meliloti LPU63 was isolated from acid topsoil (in Argentina) and showed to be a highly competitive and efficient N2-fixing rhizobium under both neutral and moderately acidic soil conditions. In this study, we obtained a draft of the LPU63 genome sequence using Illumina HiSeq4000. The whole genome phylogenetic analysis confirmed the taxonomic position of LPU63 as a S. meliloti strain and the multilocus sequence analysis confirmed that LPU63 is not related to the strains used in Argentina in bioformulations. The genomic analysis showed that beyond the canonical chromosome, pSymA, and pSymB, LPU63 strain has an accessory plasmid that codes for a repABC origin of replication and a conjugative T4SS, suggesting that this plasmid could be self-transmissible. In addition, the complete denitrification pathway (i.e., the gene clusters nap, nir, nor, and nos), including napC and nosZ, which could be used as an alternative respiration route under hypoxic conditions with moderate N2O emissions was found. Also, genes associated with plant growth-promoting activities (PGPR) and the degradation of phenylacetic acid (PAA) were identified. LPU63 is a highly melanogenic strain, a property that could enhance its survival under soil conditions, and the genome data showed a particular arrangement of the genes involved in melanin production. The information regarding LPU63 activities compatible with plant-growth promotion phenotypes, together with other characteristics mentioned here (melanin production, potential moderate N2O emissions), constitute the basis of future experiments toward the rational design of a novel bioinoculant for the environmentally sustainable production of alfalfa.

Clinically silent corticotroph tumors are usually macroadenomas that comprise 20% of ACTH tumors. They frequently progress to aggressive tumors with high recurrence, invasiveness, and on rare occasions, they may become hormonally active causing Cushing’s disease. Trustable biomarkers that can predict their aggressive course, as well as their response to traditional or new therapies, are paramount. Aberrant β-Catenin expression and localization have been proposed as responsible for several malignancies including pituitary tumors. Nevertheless, the role of β-Catenin in the aggressive transformation of silent corticotropinomas and their response to Temozolomide salvage treatment have not been explored yet. In this work, we present a case of a silent corticotroph tumor that invaded cavernous sinus and compressed optic chiasm and, after a first total resection and tumor remission it recurred six years later as an aggressive ACTH-secreting tumor. This lesion grew with carotid compromise and caused Cushing’s signs. It required multiple medical treatments including Cabergoline, Ketoconazole, TMZ, and radiotherapy. Besides, other two surgeries were needed until it could be controlled. Interestingly, we found α-SMA vascular area reduction and differential β-Catenin cell localization in the more aggressive tumor stages characterized by high Ki-67 indexes and p53 expression. Our results may indicate a role of angiogenesis and β-Catenin trigged events in the pituitary tumor progression, which could in turn affect the response to TMZ and/or conventional treatments. These molecular findings in this unusual case could be useful for future management of aggressive pituitary tumors.

The capacity of passive optical networks (PONs) is continuously increasing, and it has been standardized up to 50 Gbit/s. The two main standardization organizations, IEEE and ITU-T, are actively working on the next-generation PON, which appears to be a 100G-PON still based on intensity modulation. Even though direct detection would be preferred for its cost and simplicity, the choice of coherent detection seems inevitable when the bit rate reaches 200–400 Gbit/s, specifically to guarantee the optical power budget requirement of an access network. The introduction of coherent systems in the PON scenario, allowing high-power-budget performances, should encouragetelecom operators to merge the metro and access networks into a single domain. This paper analyzes the mentioned metro + PON convergence scenario with experimental results focusing on a 400 Gbit/s fully coherent transmission (50 GBaud PM-16QAM). We characterize three different transceivers, two of which are pre-commercials. We perform experimental demonstrations, with real urban fiber and laboratory set ups, of the metro–access convergence network in terms of the minimum OSNR value of the metro path, producing an acceptable optical power budget within the access network. Our work demonstrates feasibility of merging the metro–access network by using currently coherent optical transceivers for PON applications. [ABSTRACT FROM AUTHOR]

Sports medicine is a medical specialty that supports the performance of professional and amateur athletes while maintaining their health. Sports medicine professionals need to ensure the safe participation of athletes in sports activities achieved through a periodical preparticipation evaluation (PPE) and a regular medical monitoring of the athletes’ health in accordance with the latest recommendations regarding health condition and medical history, physical working capacity, training period and programme, recovery, nutrition, use of supplements, injuries prevention and safe return to play.In order to harmonise these national variations in the content and application of the PPE, the EFSMA Scientific and Educational Commission proposes a ‘gold standard’ for elite athletes across Europe.Important objectives of PPE are early detection and prevention of severe complications during sports activities both in leisure time and competitive sports. The PPE should entail the following diagnostic components: health status, anthropometry, functional and exercise capacity.It is of utmost importance to develop and implement preventive strategies such as the PPE. Besides monitoring the health status of athletes, the PPE plays an important role in the selection process, bringing valuable information for coaches and supporting a personalised treatment approach. Screening of athletes through a standardised digital PPE could be beneficial for a better understanding of the impact of long-term physical activity. Furthermore, PPE leads the scientific community to a way of working closer together in the interest of the athletes.

In this viewpoint we make specific recommendations that can assist and make the return to sport/exercise as safe as possible for all those impacted – from the recreational athlete to the elite athlete. We acknowledge that there are varying rules and regulations around the world, not to mention the varying philosophies and numerous schools of thought as it relates to return to sport/exercise and we have been cognisant of this in our recommendations. Despite the varying rules and circumstances around the world, we believe it is essential to provide some helpful and consistent guidance for return to training and sport for sport and exercise physicians around the world at this most difficult time. The present viewpoint provides practical and medical recommendations on the resumption to sport process.

Background: SARS-CoV-2 can lead to several systemic complications, including myocardial injuries; these might be worsened by heavy physical activity. The optimal approach to cardiac risk stratification following SARS-CoV-2 infection in athletes for a safe return to play (RTP) still needs defining. The aim of this study was to assess the prevalence of abnormal RTP test results, according to the protocol of Italian Federation of Sport Medicine (FMSI), which was endorsed by the Italian Ministry of Health, potentially representing COVID-19-associated cardiac injuries. Methods: This was a prospective, multicenter, observational study. All consecutive competitive athletes who underwent COVID-19 RTP testing protocol from 1 May to 31 July 2021, across 60 Italian Centers of Sports Medicine, were enrolled in the study. Athletes were tested at least 30 days after negativization of the nasopharyngeal swab (or immediately after negativization in professional athletes or Probable Olympians). A 12-lead electrocardiography at rest and during maximal incremental exercise test with continuous O2 saturation monitoring and an echocardiographic examination were part of the protocol. In athletes with “moderate” disease (NHI classification), 24 h ECG monitoring (to be performed on a training day) and Magnetic Resonance Imaging (MRI) were also performed. Results: A total of 4143 athletes (67.8% males and 32.2% females) (53% > 18 years, 20% 18–35 years and 16% > 35 years), from more than 40 different sport disciplines, were included in the study. The mean age was 22.5 ± 13.3 years, with ages ranging from 8 to 80 years. Of these athletes, 52.3% were asymptomatic, 46.4% manifested mild symptoms, 1.1% and 0.14% had moderate or severe symptoms, respectively, while critical illness was evident in one athlete. Abnormal echocardiographic findings were detected in 80 cases (1.9%), and pericarditis in 7 cases (0.2%); all were from mildly symptomatic athletes. Arrhythmic events were recorded in 239 athletes, with 224 (5.4%) in the exercise test and 15 (0.4%) during 24 h ECG monitoring. Ventricular arrhythmias were observed in 101 (2.4%) athletes from the total population (mostly isolated or couples of premature ventricular beats): 91 in the exercise test and 10 during 24 h ECG monitoring. Cardiac magnetic resonance was performed in 34 athletes; the presence of myocarditis was confirmed in 5 athletes (0.12% of the total population, 14.7% of athletes in which MRI was performed). Conclusions: According to our results, cardiac complications from SARS-CoV-2 in asymptomatic or mildly symptomatic competitive athletes are rare, and an RTP assessment based on symptoms and ECG-monitored exercise test would ensure a safe RTP in these athletes.

Abstract Background Leishmaniasis and Chagas disease are life-threatening illnesses caused by the protozoan parasites Leishmania spp. and Trypanosoma cruzi, respectively. They are known as “neglected diseases” due to the lack of effective drug treatments and the scarcity of research work devoted to them. Therefore, the development of novel and effective drugs is an important and urgent need. Natural products are an important source of bioactive molecules for the development of new drugs. In this study, we evaluated the activity of enhydrin, uvedalin and polymatin B, three sesquiterpene lactones (STLs) isolated from Smallanthus sonchifolius, on Leishmania mexicana (MNYC/BZ/62/M) and Trypanosoma cruzi (Dm28c). In addition, the in vivo trypanocidal activity of enhydrin and uvedalin and the effects of these STLs on parasites’ ultrastructure were evaluated. Methods The inhibitory effect of the three STLs on the growth of L. mexicana amastigotes and promastigotes as well as T. cruzi epimastigotes was evaluated in vitro. The changes produced by the STLs on the ultrastructure of parasites were examined by transmission electron microscopy (TEM). Enhydrin and uvedalin were also studied in a murine model of acute T. cruzi infection (RA strain). Serum activities of the hepatic enzymes alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were used as biochemical markers of hepatotoxicity. Results The three compounds exhibited leishmanicidal activity on both parasite forms with IC50 values of 0.42–0.54 μg/ml for promastigotes and 0.85–1.64 μg/ml for intracellular amastigotes. Similar results were observed on T. cruzi epimastigotes (IC50 0.35–0.60 μg/ml). The TEM evaluation showed marked ultrastructural alterations, such as an intense vacuolization and mitochondrial swelling in both L. mexicana promastigotes and T. cruzi epimastigotes exposed to the STLs. In the in vivo study, enhydrin and uvedalin displayed a significant decrease in circulating parasites (50–71%) and no signs of hepatotoxicity were detected. Conclusions Enhydrin, uvedalin and polymatin B possess significant leishmanicidal and trypanocidal activity on different parasite stages. These results show that these compounds may provide valuable leads for the development of new drugs against these neglected parasitic diseases.