Gingival overgrowth caused by Olmesartan Medoxomil: Observational study

Objective: Olmesartan Medoxomil is a type 1 receptor antagonist an antagonist of type 1 receptor (AT1) of angiotensin II (A-II) that inhibits numerous actions of A-II in the renin-angiotensin-aldosterone system (RAAS). A-II is a significant and multifunctional peptide involved in the pathophysiology of blood hypertension and for this reason it represents the main target in several classes of drugs used to treat and control arterial hypertension, such as angiotensin converting enzyme inhibitors (ACE-i), angiotensin receptor blockers (ARB) and renin direct inhibitors. The aim of the study is to evaluate whether the two drugs that have as an active principle Olmesartan Medoxomil, with and without the diuretic hydrochlorothiazide, are able to determine gingival overgrowth. Study Design: 108 subjects were examined and divided into three groups: G1, subjects treated with Olmesartan Medoxomil and hydrochlorothiazide (n=60); G2, subjects received only Olmesartan Medoxomil (n=24); G3, control group without pharmacological therapies (n=24). The plaque index (IP) and the gingival overgrowth index (OI) were recorded, considering the vertical and horizontal components. Results: Vertical overgrowth averaged between 0.17 \ub1 0.15 (G3) and 0.34 \ub1 0.26 (G2) showing statistically significant differences (p <0.05) compared to the other groups. Horizontal overgrowth ranged from 0.18 \ub1 0.26 (G3) to 0.49 \ub1 0.35 (G2) showing statistically significant differences (p <0.05). Conclusions: antihypertensive agents as Olmesartan Medoxomil may result in mild gingival overgrowth in the upper and lower frontal dental elements not related to other etiological factors

Reciprocal Homer1a and Homer2 Isoform Expression Is a Key Mechanism for Muscle Soleus Atrophy in Spaceflown Mice

The molecular mechanisms of skeletal muscle atrophy under extended periods of either disuse or microgravity are not yet fully understood. The transition of Homer isoforms may play a key role during neuromuscular junction (NMJ) imbalance/plasticity in space. Here, we investigated the expression pattern of Homer short and long isoforms by gene array, qPCR, biochemistry, and laser confocal microscopy in skeletal muscles from male C57Bl/N6 mice (n = 5) housed for 30 days in space (Bion-flight = BF) compared to muscles from Bion biosatellite on the ground-housed animals (Bion ground = BG) and from standard cage housed animals (Flight control = FC). A comparison study was carried out with muscles of rats subjected to hindlimb unloading (HU). Gene array and qPCR results showed an increase in Homer1a transcripts, the short dominant negative isoform, in soleus (SOL) muscle after 30 days in microgravity, whereas it was only transiently increased after four days of HU. Conversely, Homer2 long-form was downregulated in SOL muscle in both models. Homer immunofluorescence intensity analysis at the NMJ of BF and HU animals showed comparable outcomes in SOL but not in the extensor digitorum longus (EDL) muscle. Reduced Homer crosslinking at the NMJ consequent to increased Homer1a and/or reduced Homer2 may contribute to muscle-type specific atrophy resulting from microgravity and HU disuse suggesting mutual mechanisms

Radiomics and artificial intelligence in prostate cancer: new tools for molecular hybrid imaging and theragnostics

In prostate cancer (PCa), the use of new radiopharmaceuticals has improved the accuracy of diagnosis and staging, refined surveillance strategies, and introduced specific and personalized radioreceptor therapies. Nuclear medicine, therefore, holds great promise for improving the quality of life of PCa patients, through managing and processing a vast amount of molecular imaging data and beyond, using a multi-omics approach and improving patients' risk-stratification for tailored medicine. Artificial intelligence (AI) and radiomics may allow clinicians to improve the overall efficiency and accuracy of using these "big data" in both the diagnostic and theragnostic field: from technical aspects (such as semi-automatization of tumor segmentation, image reconstruction, and interpretation) to clinical outcomes, improving a deeper understanding of the molecular environment of PCa, refining personalized treatment strategies, and increasing the ability to predict the outcome. This systematic review aims to describe the current literature on AI and radiomics applied to molecular imaging of prostate cancer

DESLOCAMENTO DO DISCO ARTICULAR SEM REDUÇÃO

As desordens temporomandibulares (DTM) referem-se a um conjunto de condições que afetamos músculos da mastigação e/ou a articulação temporomandibular (ATM). O deslocamentodo disco da articulação temporomandibular tem sido definido como uma relação anormal dodisco articular com o côndilo mandibular, fossa e eminência articulares. O objetivo deste estudofoi relacionar os conceitos e características do deslocamento do disco articular sem redução.O estudo foi realizado por meio de um levantamento bibliográfico no qual se constatou queos sinais e os sintomas das disfunções musculares e articulares relacionados à articulaçãotemporomandibular e à mastigação são considerados como um grupo heterogêneo deproblemas de saúde relacionados à dor crônica. O deslocamento de disco com redução podeter uma evolução de agravamento fisiopatológico para o deslocamento de disco sem redução,caracterizado pelo deslocamento permanente do disco articular. Um dos sinais mais frequentesé o desvio da trajetória na abertura mandibular para a linha média do lado da articulaçãoafetada. Os côndilos não conseguem recapturar o disco com movimento; não há redução epor isso não ocorrem ruídos articulares. Os tecidos retrodiscais são altamente inervados evascularizados, se o côndilo comprimir essa região, pode provocar dor, inflamação e efeitosexcitatórios. A abordagem terapêutica deve iniciar-se pelos métodos não invasivos, como aterapia educacional do paciente, a terapia farmacológica, a terapia física e as goteiras oclusais.Apenas quando essa abordagem não promove uma melhoria dos sinais e sintomas é que sedeve considerar avançar para uma abordagem cirúrgica. Ao fim do estudo, constatou-se quesão necessárias investigações futuras que foquem o estudo da biomecânica e dos evento

The Ca2+-activated Cl- channel TMEM16B regulates action potential firing and axonal targeting in olfactory sensory neurons

The Ca(2+)-activated Cl(-) channel TMEM16B is highly expressed in the cilia of olfactory sensory neurons (OSNs). Although a large portion of the odor-evoked transduction current is carried by Ca(2+)-activated Cl(-) channels, their role in olfaction is still controversial. A previous report (Billig et al. 2011. Nat. Neurosci. http://dx.doi.org/10.1038/nn.2821) showed that disruption of the TMEM16b/Ano2 gene in mice abolished Ca(2+)-activated Cl(-) currents in OSNs but did not produce any major change in olfactory behavior. Here we readdress the role of TMEM16B in olfaction and show that TMEM16B knockout (KO) mice have behavioral deficits in odor-guided food-finding ability. Moreover, as the role of TMEM16B in action potential (AP) firing has not yet been studied, we use electrophysiological recording methods to measure the firing activity of OSNs. Suction electrode recordings from isolated olfactory neurons and on-cell loose-patch recordings from dendritic knobs of neurons in the olfactory epithelium show that randomly selected neurons from TMEM16B KO mice respond to stimulation with increased firing activity than those from wild-type (WT) mice. Because OSNs express different odorant receptors (ORs), we restrict variability by using a mouse line that expresses a GFP-tagged I7 OR, which is known to be activated by heptanal. In response to heptanal, we measure dramatic changes in the firing pattern of I7-expressing neurons from TMEM16B KO mice compared with WT: responses are prolonged and display a higher number of APs. Moreover, lack of TMEM16B causes a markedly reduced basal spiking activity in I7-expressing neurons, together with an alteration of axonal targeting to the olfactory bulb, leading to the appearance of supernumerary I7 glomeruli. Thus, TMEM16B controls AP firing and ensures correct glomerular targeting of OSNs expressing I7. Altogether, these results show that TMEM16B does have a relevant role in normal olfaction

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Loss of FGFR4 promotes the malignant phenotype of PDAC

Transcriptomic analyses of pancreatic ductal adenocarcinoma (PDAC) have identified two major epithelial subtypes with distinct biology and clinical behaviours. Here, we aimed to clarify the role of FGFR1 and FGFR4 in the definition of aggressive PDAC phenotypes. We found that the expression of FGFR4 is exclusively detected in epithelial cells, significantly elevated in the classical PDAC subtype, and associates with better outcomes. In highly aggressive basal-like/squamous PDAC, reduced FGFR4 expression aligns with hypermethylation of the gene and lower levels of histone marks associated with active transcription in its regulatory regions. Conversely, FGFR1 has more promiscuous expression in both normal and malignant pancreatic tissues and is strongly associated with the EMT phenotype but not with the basal-like cell lineage. Regardless of the genetic background, the increased proliferation of FGFR4-depleted PDAC cells correlates with hyperactivation of the mTORC1 pathway both in vitro and in vivo. Downregulation of FGFR4 in classical cell lines invariably leads to the enrichment of basal-like/squamous gene programs and is associated with either partial or full switch of phenotype. In sum, we show that endogenous levels of FGFR4 limit the malignant phenotype of PDAC cells. Finally, we propose FGFR4 as a valuable marker for the stratification of PDAC patients

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Effect of platelet rich plasma in non surgically treated chronic Achilles tendon ruptures

Background: Achille's tendon ruptures are relatively common among foot and ankle injuries. They are considered chronic when last beyond 4-6 weeks from the time of injuries. The management of chronic ruptures is usually different from the acute ones, and although the optimal treatment is controversial, it is common opinion that surgical treatment is the main stay of therapy. Platelet rich therapies are becoming of common use in clinical practice to treat musculotendinous injuries and in some cases, platelet rich plasma has been used as additional therapy when surgery is performed. In this study, we propose the results of a small clinical series in which PRP is used as main treatment in chronic Achille's tendon ruptures. Methods: Between May 2020 and March 2022, five patients with chronic Achille's tendon rupture underwent platelet rich therapy in association with the use of a functional ankle bracing system with wedges for the first 8 weeks. Pre- and post-treatment data were collected with ATRS and AOFAS scores as primary outcomes and heel rise tests as secondary outcomes. Results: there was relevant improvement from pre-treatment to post-treatment clinical and functional outcomes. The AOFAS mean scores gradually improved from 54 in pre-treatment to 100 in post-treatment follow-up (p < 0,001). Heel rise and height significantly increased at the final follow-up. Also, ATRS increased from 23 to 98 at the last follow-up. Conclusion: to our knowledge, this is the first report on PRP use without surgical treatment of a chronic and complete rupture of Achille’s tendon. The reported outcomes (ATRS AOFAS) evidence an improvement during follow-up; the results are in line with those expected after surgical treatment indeed, patients return to their work and sport activity practised before the injury. Level of Evidence: IV, prospective case serie

Magnetic resonance imaging in patients with nipple discharge: should we recommend it?

OBJECTIVES: Comparing the sensitivity of Contrast-Enhanced Magnetic Resonance Imaging (CEMRI), mammography and ultrasonography in patients with nipple discharge (ND). METHODS: We retrospectively evaluated 38 women with ND who underwent mammography, ultrasound and 1.5 T CEMRI between March 2007 and July 2009. Imaging findings, pathological diagnosis and follow-up data (mean follow-up: 20 months) were compared. Sensitivity and specificity values were reckoned. Statistical differences in sensitivity were assessed. RESULTS: 5/38 malignancies (13.2%; 3 invasive, 2 intraductal; 4 ipsilateral, 1 contralateral to ND), and 14/38 High-Risk Lesion (HRL--36.8%; 11 intraductal papillomas, 1 papilloma with LCIS, 1 sclerosing papilloma and 1 atypical intraductal hyperplasia, all ipsilateral) were found. CEMRI identified 5/5 cancers and 13/14 HRL (Overall Sensitivity-OSS = 94.7%; Overall Specificity-OSP = 78.9%). 3/5 cancers (1 invasive, 1 in-situ; 1 invasive contralateral) and 2/14 HRL were detected by CEMRI only. Mammography found 2/5 cancer and 3/14 HRL (OSS = 26.3%; OSP = 94.7%). Ultrasound identified 1/5 cancer and 11/14 HRL (OSS = 63.2%; OSP = 84.2). 1/14 HRL was detected by ultrasound only. Compared with mammography and ultrasound, CEMRI showed statistically significantly higher OSS values (p < 0.0001, p = 0.042 respectively). CONCLUSION: In women with ND, CEMRI should be recommended when conventional imaging is negative. Unexplained ND could be considered an indication for CEMRI