A neural circuit for male sexual behavior and reward.

Male sexual behavior is innate and rewarding. Despite its centrality to reproduction, a molecularly specified neural circuit governing innate male sexual behavior and reward remains to be characterized. We have discovered a developmentally wired neural circuit necessary and sufficient for male mating. This circuit connects chemosensory input to BNSTprTac1 neurons, which innervate POATacr1 neurons that project to centers regulating motor output and reward. Epistasis studies demonstrate that BNSTprTac1 neurons are upstream of POATacr1 neurons, and BNSTprTac1-released substance P following mate recognition potentiates activation of POATacr1 neurons through Tacr1 to initiate mating. Experimental activation of POATacr1 neurons triggers mating, even in sexually satiated males, and it is rewarding, eliciting dopamine release and self-stimulation of these cells. Together, we have uncovered a neural circuit that governs the key aspects of innate male sexual behavior: motor displays, drive, and reward.

BUB1B monoallelic germline variants contribute to prostate cancer predisposition by triggering chromosomal instability.

BACKGROUND: Prostate cancer (PrCa) is the most frequently diagnosed cancer in men. Variants in known moderate- to high-penetrance genes explain less than 5% of the cases arising at early-onset (< 56 years) and/or with familial aggregation of the disease. Considering that BubR1 is an essential component of the mitotic spindle assembly checkpoint, we hypothesized that monoallelic BUB1B variants could be sufficient to fuel chromosomal instability (CIN), potentially triggering (prostate) carcinogenesis. METHODS: To unveil BUB1B as a new PrCa predisposing gene, we performed targeted next-generation sequencing in germline DNA from 462 early-onset/familial PrCa patients and 1,416 cancer patients fulfilling criteria for genetic testing for other hereditary cancer syndromes. To explore the pan-cancer role of BUB1B, we used in silico BubR1 molecular modeling, in vitro gene-editing, and ex vivo patients' tumors and peripheral blood lymphocytes. RESULTS: Rare BUB1B variants were found in ~ 1.9% of the early-onset/familial PrCa cases and in ~ 0.6% of other cancer patients fulfilling criteria for hereditary disease. We further show that BUB1B variants lead to decreased BubR1 expression and/or stability, which promotes increased premature chromatid separation and, consequently, triggers CIN, driving resistance to Taxol-based therapies. CONCLUSIONS: Our study shows that different BUB1B variants may uncover a trigger for CIN-driven carcinogenesis, supporting the role of BUB1B as a (pan)-cancer predisposing gene with potential impact on genetic counseling and treatment decision-making.

Might photobiomodulation therapy interfere with the frequency of severe mucositis and oral candidiasis? A retrospective analysis in patients with head and neck carcinoma.

PURPOSE: Considering the tumor in the oral cavity or the oropharynx and nasopharynx region might be an aggravating factor for oral mucositis (OM) manifestation, the present study aimed to evaluate whether the location of the tumor and the use of photobiomodulation therapy (PBMT) might affect the frequency of oral candidiasis (OC) during radiotherapy (RT) and/or chemotherapy (CT) treatments. METHODS: The medial records of seventy-four patients with head and neck cancer treated in a public service from 2016 to 2019 were evaluated. All these patients were submitted to RT in an accumulated dose of 48 to 70 Gy of radiation. Data about OM and OC were collected and presented according to the application of a therapeutic protocol with laser photobiomodulation (PBMT) to control oral mucositis, or not (No-PBM), and the location of tumor (head and neck or oral cavity). In the PBMT group patients, a low-power laser device composed of InGaAlP diode (maximum output power of 86.7 mW, active tip area of 0.1256 cm2, and continuous wavelength of 660 nm), was applied to the lips (three points each), right and left jugal mucosa (three points each), the limit between hard and soft palate (three points), buccal floor/sublingual gland (one point), lateral edge of the tongue (three points on each side), and back of the tongue (six points), three times weekly, for 5 weeks. The dosimetry used in each application was 2 J for 3 s, thus totaling 56 J. The correlation between clinical characteristics such as age, tumor size (T), metastatic lymph node (N), number of RT and CT sessions, candidiasis, and OM were analyzed. RESULTS: Mucositis grades 1 and 2 were the most common among all patients, especially before the 12th radiotherapy session, regardless of the treatment with PBM (p > 0.05). Additionally, no difference in the grade of OM and OC was significantly observed when comparing the two laser therapy groups. OC was more frequent after the 12th radiotherapy session in all groups. Nonetheless, OM and OC had a different correlation regarding to tumor location (head and neck and oral cavity) being PBMT a positive therapy to delay OM. It was observed a positive and statistically significant correlation between tumors at oral cavity and OM, regardless PBMT (R = 0.84, p < 0.05 to PBMT and R = 0.13, p < 0.05 to No-PBM). Otherwise, OC was positively correlated to local metastasis in patients with oral tumors undergoing PBMT (R = 0.84, p < 0.05). CONCLUSION: Patients with oral cavity tumor presented more OM, especially high grades, then patients with tumors in other regions of the head and neck, which seems to be related to the irradiation parameters of radiotherapy and/or with the limitation of conduction of PBMT in tumor areas. OM and OC were not changed by PBMT, although it helped to reduce the incidence of severe cases of OM.

Impact of cervicovaginal microbiome on the risk of cervical abnormalities development.

The vaginal microbiome has emerged as potentially influencing the natural history of Human Papillomavirus (HPV) infections and their clinical impact. We aimed to characterize the vaginal microbiome in samples from 807 high-risk HPVs (Hr-HPV) positive women with a mean age of 41.45 ± 10.79 years who participated in the Regional Cervical Cancer Screening Program from the Northern Region of Portugal. Microbiome analysis was performed with commercial kits for the detection of 21 microorganisms. The most frequent microorganisms were Ureaplasma parvum (52.5%), Gardnerella vaginalis (GV) (34.5%), Atopobium vaginae (AV) (32.6%), Lacto (30.7%), and Mycoplasma hominis (MH) (23.5%). The distribution according to age reveals that MH, Mega1, GV, BVab2, AV, and Mob were more prevalent in women older than 41 years of age (p < 0.050), while Lacto is significantly decreased in this group (23.5% vs. 39.4%, p < 0.001; RR = 0.47). The risk analysis showed that Hr-HPV-16/-18 and Hr-HPV-9val genotypes are associated with an increased risk of developing cervical abnormalities, while Lacto (p < 0.001; odd ratio [OR] = 0.33), GV (p = 0.0111; OR = 0.41), AV (p = 0.033; OR = 0.53) and Mob (p = 0.022; OR = 0.29) are associated with protection. Similar results were found for the risk of development atypical squamous cells cannot exclude HSIL/high-grade squamous intraepithelial lesion. Overall, the multivariate analysis confirmed that lactobacillus and bacteria associated with bacterial vaginosis (GV, AV, and Mob) are associated with protection against the development of cervical abnormalities. This study provides important data to be included in the future management of risk stratification for Hr-HPV-positive women.

Impact of high-risk Human Papillomavirus genotyping in cervical disease in the Northern region of Portugal: Real-world data from regional cervical cancer screening program.

Cervical cancer prevention is based on primary prevention with vaccines against Human Papillomavirus (HPV) and secondary prevention by screening with High-Risk-HPV (Hr-HPV) detection. Since 2017, cervical cancer screening in women aged 25-60 years has been performed in Portugal using Hr-HPV detection, followed by cytology in Hr-HPV-positive cases. Herein we report the prevalence of Hr-HPV genotypes and cytological abnormalities among 462 401 women (mean age: 43.73 ± 10.79; median age: 45; range: 24-66 years) that participated in the Regional Cervical Cancer Screening Program of the Northern Region of Portugal, performed between August 2016 and December 2021. Overall, we describe a prevalence rate of 12.50% for Hr-HPV varying from 20.76% at age 25% to 8.32% at age 64. The five most common Hr-HPV genotypes identified were HPV-68 (16.09%), HPV-31 (15.30%), HPV-51 (12.96%), HPV-16 (11.06%), and HPV-39 (11.01%). The prevalence of Hr-HPV included in the nonavalent vaccine (HPV-9valent) was 55.00% ranging from 47.78% to 59.18% across different age groups. Considering positive Hr-HPV cases, 65.68% had a Negative for Intraepithelial Lesion or Malignancy (NILM) cytology, 20.83% atypical squamous cells of undetermined significance (ASC-US), 8.85% Low-Grade Squamous Intraepithelial Lesion (LSIL), 1.65% High-Grade Squamous Intraepithelial Lesion (HSIL), 2.85% ASC-H, 0.09% Atypical Glandular Cells, 0.02% Adenocarcinomas, and 0.02% Squamous Cell Carcinoma (SCC). Our analysis revealed that HPV-9val genotypes were responsible for 52.13% NILM, 59.21% ASC-US, 55.06% LSIL, 90.14% HSIL, 83.50% ASC-H, and 100.00% SCC. Furthermore, multiple Hr-HPV infections (risk ratio [RR] = 1.46; 95% confidence interval [CI] 1.34-1.58), HPV-16/18 (RR = 5.16; 95% CI 4.75-5.93), or HPV-9val genotypes (RR = 5.23; 95% CI 4.68-5.85) were associated with a significant risk of developing > HSIL (p < 0.001). To date, this is the largest study on Hr-HPV genotyping in cervical cancer screening that includes data from a complete cycle of the screening program. Our findings suggest a high prevalence of HPV-9valent genotypes and a significant association with an increased risk of developing > HSIL. This constitutes important data for health authorities, which may help define the future of vaccination and cervical cancer screening strategies.

Evaluation of New Potential Inflammatory Markers in Patients with Nonvalvular Atrial Fibrillation.

Atrial fibrillation (AF), the most common arrhythmia in clinical practice, is associated with an increase in mortality and morbidity due to its high potential to cause stroke and systemic thromboembolism. Inflammatory mechanisms may play a role in the pathogenesis of AF and its maintenance. We aimed to evaluate a range of inflammatory markers as potentially involved in the pathophysiology of individuals with nonvalvular AF (NVAF). A total of 105 subjects were enrolled and divided into two groups: patients with NVAF (n = 55, mean age 72 ± 8 years) and a control group of individuals in sinus rhythm (n = 50, mean age 71 ± 8 years). Inflammatory-related mediators were quantified in plasma samples by using Cytometric Bead Array and Multiplex immunoassay. Subjects with NVAF presented significantly elevated values of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF), interferon-gamma, growth differentiation factor-15, myeloperoxidase, as well as IL-4, interferon-gamma-induced protein (IP-10), monokine induced by interferon-gamma, neutrophil gelatinase-associated lipocalin, and serum amyloid A in comparison with controls. However, after multivariate regression analysis adjusting for confounding factors, only IL-6, IL-10, TNF, and IP-10 remained significantly associated with AF. We provided a basis for the study of inflammatory markers whose association with AF has not been addressed before, such as IP-10, in addition to supporting evidence about molecules that had previously been associated with the disease. We expect to contribute to the discovery of markers that can be implemented in clinical practice hereafter.

Toxicity of Heavy Metals that Affect Germination, Development and Cell Cycle of Allium cepa L.

This study aimed to investigate the impact of heavy metals copper, cadmium, lead, aluminum and nickel, on the growth, physiology, metabolism, and cell cycle of Allium cepa L. Five treatments with increasing concentrations (0, 50, 100, 250, and 500 µM) were applied to the seeds. The results showed that the highest concentrations of copper and cadmium had phytotoxic and biochemical effects on the onion. Additionally, copper concentrations caused an increase in mitodepressive effect and chromosomal abnormalities. Aluminum also induced several chromosomal abnormalities. The study found that Cd > Cu > Pb > Ni > Al and Cu > Al > Ni > Pb > Cd had the highest phytotoxic and cytotoxic potentials, respectively. Furthermore, the UPGMA method revealed three divergent groups. These results suggest that heavy metals, especially copper, have a significant pollution potential when present in high concentrations.

Editor's Choice - Systematic Review and Meta-Analysis of Normal Infrarenal Aortic Diameter in the General Worldwide Population and Changes in Recent Decades.

OBJECTIVE: To analyse the characteristics of normal infrarenal aortic diameter (AD) in the general worldwide population, to examine changes over time, and to investigate geographical differences. DATA SOURCES: PubMed, Cochrane Library, and Web of Science. REVIEW METHODS: This was a systematic review and meta-analysis of studies published up to October 2020 describing infrarenal AD measured by ultrasound in the general adult population. The study was conducted in accordance with the PRISMA statement and placed no restrictions on geographical location or year of publication. Studies of individuals pre-selected for certain diseases or risk factors and opportunistic screening were excluded. A random effects model was used to estimate pooled mean AD, and meta-regression analysis was used to study the effects of determinants of AD. RESULTS: Thirty-two studies were included, reporting data for 941 144 individuals (98% were men). The pooled mean AD was 19.4 mm (95% confidence interval [CI] 18.8 - 20.1), being 20.1 mm (95% CI 19.4 - 20.8) in men and 17.8 mm (95% CI 16.5 - 19.1) in women (p < .001). Outer edge to outer edge (OTO) caliper placement method (p = .015) and body surface area (BSA; p = .010) were significantly associated with larger AD. In men, the largest mean AD was observed in Oceania (p < .001) and the smallest in Asia (p < .020). As none of the studies collected data between 2002 and 2007, the studies were divided into two periods: 2001 and before, and 2008 and after. All recent studies were European, with the diameters being significantly smaller (p = .003) in the latter period (18.3 mm [95% CI 17.5 - 19.1] vs. 20.7 mm [95% CI 19.1 - 22.3]). In the meta-regression models, the reduction in AD over time remained significant after adjustment for potential effect modifiers such as sex, age, geographical area, body size, cardiovascular risk factors, and ultrasound method. CONCLUSION: Mean infrarenal AD in older European adults has decreased significantly in recent decades. Male sex, BSA, and OTO ultrasound measurement method are associated with larger AD, and geographical differences were observed in men.

Evaluation of serum haptoglobin levels and Hp1-Hp2 polymorphism in the haptoglobin gene in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is an arrhythmia that involves structural and electrophysiological abnormalities. Many of the AF-related clinical conditions are associated with an increase in inflammatory and oxidative factors. Haptoglobin (Hp) is an acute phase protein whose biological role is to promote clearance of free hemoglobin (Hb). In addition, for being considered an inflammatory marker, Hp represents a protective mechanism against the oxidative effects of Hb. The Hp1-Hp2 polymorphism at Hp locus can lead to three phenotypes related to structural and functional differences in the protein. The objective of this study were to evaluate Hp levels and Hp1-Hp2 polymorphism at Hp locus in patients with AF compared to a control group. METHODS AND RESULTS: This study included 65 patients with AF and 54 individuals without the arrhythmia. Biochemical parameters were determined using Vitros system, plasma levels of Hp were measured in serum samples by using ELISA method and polymorphisms were verified by PCR technique. Plasma Hp levels, as well as allelic and genotypic frequency, were not associated with AF. The levels of Hp also did not differ among the genotypes according to the applied models. CONCLUSIONS: The results suggest that Hp levels and Hp1-Hp2 polymorphism are not associated to AF.

Impact of photobiomodulation for oral mucositis on body weight and BMI of patients with head and neck cancer.

PURPOSE: To evaluate the impact of photobiomodulation for oral mucositis on body weight and body mass index (BMI) in head and neck cancer patients. METHODS: Patients were separated into two groups: photobiomodulation (PBM) (n = 17) and SHAM (n = 19). Participants assigned to the PBM group received the photobiomodulation therapy on alternate days at 33 different sites of the oral mucosa (1 J for 10 s per application point) using a low-power aluminum gallium arsenide (AsGaAl) laser device with a maximum output power of 86.7 mW and a wavelength of 660 nm (red). The same protocol was performed in patients allocated in the SHAM group but with the device turned off. At the first and twenty-fourth radiotherapy sessions, participants from both groups underwent an intraoral examination to assess the presence or absence of mucositis using the WHO scale, and measurements of weight and height for BMI calculation were undertaken. RESULTS: All patients had significant differences in weight and BMI throughout the study period. Patients in the PBM group lost less weight (p < 0.01) and had a reduced BMI loss (p < 0.01) in comparison to patients in the SHAM group. Although PBM did not prevent oral mucositis, it decreased its severity (p < 0.01). CONCLUSION: Photobiomodulation for oral mucositis reduced weight loss and prevented a reduction in BMI in patients who underwent chemoradiotherapy for head and neck cancer. Retrospectively registered at https://data.mendeley.com//datasets/4kd7s49wk4/1 .

Characteristics and management of Susac syndrome in an emergent country: a multi-center case series from Brazil.

BACKGROUND: Susac syndrome (SS) is a rare endotheliopathy with an estimated prevalence of 0.14-0.024 per 100,000. It is an important differential diagnosis in demyelinating disorders. There are few case series and no large randomized controlled trials, and most reports come from developed countries. We report six cases of SS in three centers in Brazil and discuss management challenges in emergent countries. METHODS: This is a retrospective case series of patients diagnosed with SS in three medical centers in Brazil between April 2018 and July 2021. The European Susac consortium (EuSaC) criteria were used for diagnosis of SS. Demographic data and clinical interventions were described and outcomes were assessed subjectively and by applying the modified Rankin Scale (mRS) on last follow-up. RESULTS: Six patients were diagnosed with SS (3 males, 3 females). Mean age at presentation was 36 years (range 17 to 54). The most common initial symptom was confusion, followed by visual impairment and hearing loss. Characteristic snowball lesions on magnetic resonance imaging (MRI) were present in four patients (66%). Retinal artery abnormalities were present in half (3/6) of patients, and sensorineural hearing loss was present in four patients (66%). Outcome was favorable (mRS ≤ 2) in five patients (86%). Patients treated early had a more favorable outcome. CONCLUSION: Emergent countries face challenges in the diagnosis and management of patients with SS, such as access to advanced tests (fluorescein angiography, serial MRI) and treatment drugs (rituximab, mycophenolate). Further research should consider particularities of patients with SS in emergent countries.

Action of Matricaria recutita (chamomile) in the management of radiochemotherapy oral mucositis: A systematic review.

The objective of this study was to evaluate the effect of topical chamomile in the prevention and/or treatment of oral mucositis (OM) in cancer patients. It was a systematic review, which sought articles of the randomized clinical trial according to the PRISMA parameters, registered in the PROSPERO. The databases used were PubMed, Cochrane Library, and Bireme. Descriptors were selected from DeCs/MeSH and the PICO strategy was applied. The search found 148 publications. After all the steps, six articles were selected. The total sample included 492 patients and all studies used the same OM measurement scale. The results showed that the application of topical chamomile was effective in the prevention and/or treatment of OM in four of the six studies, with a dose ranging from 1% to 2.5% and duration that ranged from single to 4 times a day. Some limitations were observed: the minimum age of the patients was not informed, and there was no specification of the sites involved or the chemotherapies used. The application of topical chamomile in the preventive/therapeutic of chemo-induced OM seems to be recommended. In addition, scientific production should be encouraged, as it aims to determine useful protocols for this phytotherapy for the oncology population.

Sarcopenia, oxidative stress and inflammatory process in muscle of cirrhotic rats - Action of melatonin and physical exercise.

Sarcopenia is one of the most common features of cirrhosis, contributing to morbidity and mortality in this population. We aimed to evaluate the effect of melatonin (MLT) and exercise (EX) on the quadriceps muscle in rats with biliary cirrhosis induced by bile duct ligation (BDL). We used 48 males (mean weight = 300 g), divided into eight groups. A 20 mg/Kg MLT dose was administered via i.p. (1 x daily), and the EX, the animals were set to swim in couples for 10 min each day. Upon completion, blood, liver, and quadriceps samples were taken for analysis. In the liver enzymes analysis and comet assay results, a reduction was observed in the groups treated with MLT with/or EX comparing to the BDL group. In the evaluation of substances that react to thiobarbituric acid (TBARS), nitric oxide levels (NO), and tumor necrosis factor-alpha levels (TNF-α), there was a significant increase in the BDL group and a reduction in the treated groups. In the activity of the superoxide dismutase enzyme (SOD) and interleukin-10 levels (IL-10) concentrations, there was a significant increase in the treated groups of the BDL group. Histological analysis revealed muscle hypotrophy in the BDL group in comparison with the control group (CO) and increased muscle mass in the treated groups. There was an increase in weight gain and phase angle in the groups treated with MLT with/or EX comparing to the BDL group. We suggest that treatments may contribute to the reduction of muscle changes in cirrhotic patients.

Geometric, Biomechanic and Haemodynamic Aortic Abnormalities Assessed by 4D Flow Cardiovascular Magnetic Resonance in Patients Treated by TEVAR Following Blunt Traumatic Thoracic Aortic Injury.

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) is widely used for the treatment of patients with blunt traumatic thoracic aortic injury (BTAI). However, aortic haemodynamic and biomechanical implications of this intervention are poorly investigated. This study aimed to assess whether patients treated by TEVAR following BTAI have thoracic aortic abnormalities in geometry, stiffness, and haemodynamics. METHODS: Patients with BTAI treated by TEVAR at Vall d'Hebron Hospital between 1999 and 2019 were compared with propensity score matched healthy volunteers (HVs). All subjects underwent cardiovascular magnetic resonance (CMR) comprising a 4D flow CMR sequence. Spatially resolved aortic diameter, length, volume, and curvature were assessed. Pulse wave velocity, distensibility, and longitudinal strain (all measurements of aortic stiffness) were determined regionally. Moreover, advanced haemodynamic descriptors were quantified: systolic flow reversal ratio (SFRR), quantifying backward flow during systole, and in plane rotational flow (IRF), measuring in plane strength of helical flow. RESULTS: Twenty-six BTAI patients treated by TEVAR were included and matched with 26 HVs. They did not differ in terms of age, sex, and body surface area. Patients with TEVAR had a larger and longer ascending aorta (AAo) and marked abnormalities in local curvature. Aortic stiffness was greater in the aortic segments proximal and distal to TEVAR compared with controls. Moreover, TEVAR patients presented strongly altered flow dynamics compared with controls: a reduced IRF from the distal AAo to the proximal descending aorta and an increased SFRR in the whole thoracic aorta. These differences persisted adjusting for cardiovascular risk factors and were independent of time elapsed since TEVAR implantation. CONCLUSION: At long term follow up, previously healthy patients who underwent TEVAR implantation following BTAI had increased diameter, length and volume of the ascending aorta, and increased aortic stiffness and abnormal flow patterns in the whole thoracic aorta compared with matched controls. Further studies should address whether these alterations have clinical implications.

Thrombin Generation and other hemostatic parameters in patients with atrial fibrillation in use of warfarin or rivaroxaban.

Patients with atrial fibrillation (AF) present hyperactivation of both platelets and coagulation leading to a hypercoagulable state which contributes to an increased risk of thromboembolism. Therefore, one of the main strategies for treatment of AF is prevention of these events through the use of oral anticoagulants (OAC). The aim of this study was to evaluate hemostasis as a whole in patients with non-valvular AF undergoing warfarin or rivaroxaban by thrombin generation test (TGT), in addition to monocyte-platelet aggregates (MPA), glycoprotein IIb/IIIa (GPIIb/IIIa), and platelet (PMP) and endothelium (EMP) microparticles, compared to age and sex matched controls. PT/INR for OAC use was also determined. In patients taking OAC, compared to control group, a decrease in TGT (p = 0.000 for all parameters) were observed. Patients taking warfarin showed to be more hypocoagulable, presenting lower levels of ETP (p = 0.000) and peak (p = 0.002) than patients using rivaroxaban. Patients on warfarin use with INR > 3 had also lower levels of ETP (p = 0.01) and peak (p = 0.006). A decrease in ETP (p = 0.03) and peak (p = 0.02) values was also observed in patients using rivaroxaban with PT > 21.4 s. Patients using warfarin (p = 0.000) and rivaroxaban (p = 0.000) presented lower levels of MPA in relation to control group. It was also observed in patients using warfarin, lower GPIIb/IIIa levels in relation to control group (p = 0.011). Patients taking rivaroxaban (p = 0.003) and warfarin (p = 0.001) had higher PMP levels compared to control group. There was no difference in levels of EMP between the groups (p = 0.0536). The present study reinforces the usefulness of OAC in AF, which decisively contribute to a better management of the disease preventing possible complications.

Biosensors for European Zoonotic Agents: A Current Portuguese Perspective.

Emerging and recurrent outbreaks caused by zoonotic agents pose a public health risk. They result in morbidity and mortality in humans and significant losses in the livestock and food industries. This highlights the need for rapid surveillance methods. Despite the high reliability of conventional pathogen detection methods, they have high detection limits and are time-consuming and not suitable for on-site analysis. Furthermore, the unpredictable spread of zoonotic infections due to a complex combination of risk factors urges the development of innovative technologies to overcome current limitations in early warning and detection. Biosensing, in particular, is highlighted here, as it offers rapid and cost-effective devices for use at the site of infection while increasing the sensitivity of detection. Portuguese research in biosensors for zoonotic pathogens is the focus of this review. This branch of research produces exciting and innovative devices for the study of the most widespread pathogenic bacteria. The studies presented here relate to the different classes of pathogens whose characteristics and routes of infection are also described. Many advances have been made in recent years, and Portuguese research teams have increased publications in this field. However, biosensing still needs to be extended to other pathogens, including potentially pandemic viruses. In addition, the use of biosensors as part of routine diagnostics in hospitals for humans, in animal infections for veterinary medicine, and food control has not yet been achieved. Therefore, a convergence of Portuguese efforts with global studies on biosensors to control emerging zoonotic diseases is foreseen for the future.

Idiopathic right common iliac artery aneurysm in a three-year-old child - case report.

The incidence of iliac aneurysms in children is unknown and there are only a small number of case reports in the literature on the subject. This article describes the case of a 3-year-old male patient with an isolated saccular aneurysm at the bifurcation of the right common iliac artery, of idiopathic origin, which was repaired by resection, ligature of the internal iliac artery and end-to-end vascular anastomosis. After 1 month of follow-up, he was diagnosed with asymptomatic occlusion of the anastomosis. The occlusion had no clinical repercussions because of collateral circulation and the child has had a favorable clinical course over the medium term.

Elucidating the mechanisms of action of parecoxib in the MG-63 osteosarcoma cell line.

Different types of tumors often present an overexpression of cyclooxygenase-2. The aim of this study was to evaluate the effects of parecoxib (NSAID, cyclooxygenase-2 selective inhibitor) in the behavior of the human osteosarcoma MG-63 cell line, concerning several biological features. Cells were exposed to several concentrations of parecoxib for 48 hours. Cell viability/proliferation, cyclooxygenase-2 expression, morphologic alterations, membrane integrity, cell cycle evaluation, cell death and genotoxicity were evaluated. When compared with untreated cells, parecoxib led to a marked decrease in cell viability/proliferation, in COX-2 expression and changes in cell morphology, in a concentration-dependent manner. Cell recuperation was observed after incubation with drug-free medium. Parecoxib exposure increased lactate dehydrogenase release, an arrest of the cell cycle at S-phase and G2/M-phase, as well as growth of the sub-G0/G1-fraction and increased DNA damage. Parecoxib led to a slight increase of necrosis regulated cell death in treated cells, and an increase of autophagic vacuoles, in a concentration-dependent manner. In this study, parecoxib showed antitumor effects in the MG-63 human osteosarcoma cells. The potential mechanism was inhibiting cell proliferation and promoting necrosis. These results further suggested that parecoxib might be a potential candidate for in-vivo studies.

Inflammatory and Infectious Processes Serve as Links between Atrial Fibrillation and Alzheimer's Disease.

Atrial fibrillation (AF) is one of the most prevalent forms of arrhythmia that carries an increased risk of stroke which, in turn, is strongly associated with cognitive decline. The majority of dementia cases are caused by Alzheimer's disease (AD) with obscure pathogenesis. While the exact mechanisms are unknown, the role of inflammatory processes and infectious agents have recently been implicated in both AD and AF, suggesting a common link between these maladies. Here, we present the main shared pathways underlying arrhythmia and memory loss. The overlapping predictive biomarkers and emerging joint pharmacological approaches are also discussed.