Zirconia Dental Implants Surface Electric Stimulation Impact on Staphylococcus aureus.

Tooth loss during the lifetime of an individual is common. A strategy to treat partial or complete edentulous patients is the placement of dental implants. However, dental implants are subject to bacterial colonization and biofilm formation, which cause an infection named peri-implantitis. The existing long-term treatments for peri-implantitis are generally inefficient. Thus, an electrical circuit was produced with zirconia (Zr) samples using a hot-pressing technique to impregnate silver (Ag) through channels and holes to create a path by LASER texturing. The obtained specimens were characterized according to vitro cytotoxicity, to ensure ZrAg non-toxicity. Furthermore, samples were inoculated with Staphylococcus aureus using 6.5 mA of alternating current (AC). The current was delivered using a potentiostat and the influence on the bacterial concentration was assessed. Using AC, the specimens displayed no bacterial adhesion (Log 7 reduction). The in vitro results presented in this study suggest that this kind of treatment can be an alternative and promising strategy to treat and overcome bacterial adhesion around dental implants that can evolve to biofilm.

Praseodymium and warming interactions in mussels: Comparison between observed and predicted results.

Being a crucial element for technological development, praseodymium (Pr) has been increasingly used, leading to a rise in its concentration in aquatic systems. However, its potential threats to organisms remain poorly understood. Besides contamination, organisms are also threatened by climate change-related factors, including warming. It is important to evaluate how climate change-related factors may influence the effects of contaminants. To address this, histopathological and biochemical analyses were performed in adult mussels of Mytilus galloprovincialis, following a 28-day exposure to Pr (10 µg/L) and warming (4 °C increase) separately, and in combination. Additionally, biochemical and physiological alterations were analysed in the sperm of mussels after 30-min exposure to the same treatments. Furthermore, it was used the Independent Action model to predict the interaction between Pr and warming. The results showed, in the case of adults exposed to Pr, an increase in superoxide dismutase (SOD) and glutathione S-transferases (GSTs) activities. However, it was insufficient, leading to histopathological injuries, redox imbalance, and cellular damage. In the case of sperm, Pr induced an increase of mitochondrial activity and respiration rate, in response to the increase in systemic metabolic rate and oxygen demand. Warming increased the metabolism, and induced redox imbalance and cellular damage in adults. In sperm, a rise in temperature induced lipid peroxidation and a decrease in velocity. Warming induced some alterations in how adult mussels responded to Pr, activating catalase instead of SOD, and in addition to GSTs, also activated carboxylesterases. However, it was not enough to avoid redox imbalance and cellular damage. In the case of sperm, the combination induced a decrease in H2O2 production, and higher oxygen demand, which prevented the decrease in motility and velocity. This study highlights the limitations of using models and emphasizes the importance of studying the impacts of emerging contaminants, such as rare earth elements, and their combination with climate change-related factors. Under environmental conditions, chronic exposure to the combined effect of different stressors might generate impacts at higher biological levels. This may affect organisms' respiratory and filtration capacity, nutrient absorption, defence capacity against infections or diseases, and sperm viability, ultimately resulting in reduced growth and reproduction, with consequences at the population level.

A rare case of epithelioid angiosarcoma.

Epithelioid angiosarcoma is a rare high-grade vascular neoplasm with a poor prognosis. We present an anticoagulated 77-year-old man, with a history of popliteal/soleal vein thrombosis in the previous month, complaining of ipsilateral persistent lower limb pain and claudication. Absent popliteal/distal pulses prompted an arterial doppler ultrasound (DUS), revealing thrombosis of the distal superficial femoral artery and a popliteal mass. As the arterial wall's integrity could not be appropriately evaluated by DUS, adventitial cystic disease of the popliteal artery was suspected. Computed tomography angiography and magnetic resonance imaging findings were also suggestive. Due to refractory pain, he was submitted to a popliteal mass excision along with a femoral-posterior tibial bypass. Pathology revealed an epithelioid angiosarcoma. He was referred to a Sarcoma Center, requiring hospitalization for agitation and fever. A positron emission tomography (PET) scan revealed extensive lower limb disease persistence and distant metastases. He died on the 56th day after surgery. To our knowledge, there are only 15 cases of angiosarcoma of the popliteal artery described in the literature. Ours stands out as the first one unrelated to a popliteal aneurysm. Being a highly-aggressive tumor, an early diagnosis is challenging but essential to a successful treatment, warranting the need for suspicion of this neoplasm. An early core biopsy or surgical sample may expedite the diagnosis.

Depth Control of an Underwater Sensor Platform: Comparison between Variable Buoyancy and Propeller Actuated Devices.

Underwater long-endurance platforms are crucial for continuous oceanic observation, allowing for sustained data collection from a multitude of sensors deployed across diverse underwater environments. They extend mission durations, reduce maintenance needs, and significantly improve the efficiency and cost-effectiveness of oceanographic research endeavors. This paper investigates the closed-loop depth control of actuation systems employed in underwater vehicles, focusing on the energy consumption of two different mechanisms: variable buoyancy and propeller actuated devices. Using a prototype previously developed by the authors, this paper presents a detailed model of the vehicle using both actuation solutions. The proposed model, although being a linear-based one, accounts for several nonlinearities that are present such as saturations, sensor quantization, and the actuator brake model. Also, it allows a simple estimation of the energy consumption of both actuation solutions. Based on the developed models, this study then explores the intricate interplay between energy consumption and control accuracy. To this end, several PID-based controllers are developed and tested in simulation. These controllers are used to evaluate the dynamic response and power requirements of variable buoyancy systems and propeller actuated devices under various operational conditions. Our findings contribute to the optimization of closed-loop depth control strategies, offering insights into the trade-offs between energy efficiency and system effectiveness in diverse underwater applications.

The role of warming in modulating neodymium effects on adults and sperm of Mytilus galloprovincialis.

The use of rare earth elements (REEs) has been increasing and one of the most used is neodymium (Nd). Being an emergent contaminant, its negative impacts are poorly understood. Aquatic organisms are also threatened by climate change-related factors, as is the case of warming, which can change the effects of REEs. Thus, the impacts of Nd, warming, and the combination of both stressors were studied in adult mussels and sperm of the species Mytilus galloprovincialis, after an exposure period of 28 days (adults) and 30 min (sperm). The effects were evaluated through the analysis of biochemical and histopathological alterations in adults and biochemical and physiological responses given by sperm. The results showed that mussels only activated their biotransformation capacity when exposed to the stressors acting alone, which was insufficient to avoid lipid peroxidation. Furthermore, warming (alone and combined with Nd) also produces damage to proteins. The digestive gland was the most sensitive organ to Nd, presenting several histopathological alterations. In the case of sperm, all stressors induced lipid peroxidation, a higher oxygen demand, and a decrease in velocity, even if the sperm viability was maintained. It seems that warming influenced the effects of Nd to some extent. The present findings contribute significantly to the field of REEs environmental toxicology by offering valuable insights into the impacts of Nd on various biological levels of mussels. Additionally, within the context of climate change, this study sheds light on how temperature influences the effects of Nd. The obtained results indicate that both stressors can potentially compromise the overall health of mussel populations, thereby affecting other species reliant on them for food and habitat. Moreover, this study highlights impaired sperm health, which could adversely affect their reproductive capacity and ultimately lead to population decline.

Enhanced removal of rare earth elements from aqueous media: exploring the potential of AM-3 and AM-4 titanosilicates.

This study investigates the impact of three key variables on the performance of nanoporous AM-3 and layered AM-4 titanosilicates in removing nine REEs (Y, La, Ce, Pr, Nd, Eu, Gd, Tb, and Dy) from natural mineral water and identifies optimal operational conditions using Response Surface Methodology (RSM). The experimental conditions were determined by a Box-Behnken Design of 3 factors-3 levels (pH 4, 6, and 8; sorbent dose 20, 100, and 180 mg/L; and element concentration 1, 3, and 5 µmol/L). Three-dimensional response surfaces were used to assess the linear, quadratic, and interaction influences of each factor on the REEs' removal percentage. The pH was the most significant factor in the removal process using AM-3, while the sorbent dose was more important for AM-4. The results highlighted the sorbents' strong capacity for REE removal. The optimal operating conditions obtained by RSM were applied to aqueous solutions with salinity 10 (common in coastal and transitional systems) and 30 (average seawater salinity). The results showed that AM-3 has a strong potential for removing REEs in solutions with salinity 10 and 30, while AM-4 was less efficient due to competition between REEs and other ions present in the solution.

Rigid Esophagoscopy for Foreign Body Extraction: Results and Complications in the Endoscopic Era.

Introduction Rigid esophagoscopy (RE) has long been a part of otolaryngology practice. In the past decades, the procedure was less commonly performed due to the advances and availability of flexible endoscopic techniques. This study aims to describe the outcomes of RE performed to treat foreign body ingestion and to evaluate risk factors associated with postoperative complications. Methods Patients who underwent RE to treat foreign body ingestion in an otolaryngology emergency department of a Portuguese tertiary university hospital, between 2010 and 2020, were included. A total of 162 cases were analyzed, and data was collected retrospectively. Results The most common foreign bodies were meat bone (31.5%, n = 47), food impaction (28.8%, n = 43), and fish bone (19.5%, n = 29). The proximal esophagus was by far the most frequent location (80%, n = 118). Esophageal perforation occurred in 8% (13 patients), and there was a 2.5% (n = 4) mortality rate. The odds ratio of an esophageal perforation if the foreign body was completely or partially located outside the proximal esophagus was 4.67 times that of a foreign body exclusively in the proximal esophagus (OR = 4.67 [95% CI: 1.39-15.72]; p = 0.016; Fisher's exact test). Conclusion RE remains an effective and important technique in the management of ingested foreign bodies, particularly if endoscopic removal is unsuccessful. Foreign body location outside the proximal esophagus was associated with esophageal perforation.

Long-pulsed 1064nm Nd:YAG laser in the treatment of leg veins: Systematic review.

OBJECTIVE: Long-pulsed 1064 nm Nd:YAG laser can damage vessels with higher diameters and penetrate to a deeper level than other laser therapies. We aim to analyze outcomes of the treatment of leg veins with long-pulsed 1064 nm Nd:YAG laser regarding intervention protocol, technical success, clinical success, and side effects. METHODS: A research of the published literature was conducted, using PubMed and Embase databases, in April 2022. The key words used were telangiectasia, reticular veins, neodymium YAG laser, clearance, satisfaction, and treatment. PRISMA guidelines were followed. RESULTS: We included twenty-six articles, twenty-three prospective and three retrospective studies, with a total of 1991 patients. The articles were organized in different sections according to the control group. The four outcomes were analyzed in each section. These studies showed that the long-pulsed 1064 nm Nd:YAG laser is a safe and very good option for the treatment of leg veins measuring up to 3 mm in diameter. Studies comparing long-pulsed 1064 nm Nd:YAG laser therapy and sclerotherapy showed similar clearance rates with no significant differences. However, sclerotherapy seemed to be less painful and to have faster clinical improvements. In two articles, Nd:YAG laser had better outcomes in the treatment of smaller vessels with less than 1 mm in diameter, than sclerotherapy alone. Treatment with polidocanol microfoam and Nd:YAG laser had better clearance rates than Nd:YAG laser alone in three studies. In the comparison of 1064 nm Nd:YAG laser therapy with other lasers and light sources, the studies had contradictory results. CONCLUSION: Long-pulsed 1064 nm Nd:YAG laser is a valid therapeutic option for leg telangiectasia and reticular veins with great aesthetic outcomes and minor side effects. Nd:YAG laser therapy could be combined with sclerotherapy or other laser therapies or IPL in order to achieve better results. Serious side effects are rare, but the procedure is almost always accompanied by moderate tolerable pain.

Wound, Ischemia, Foot Infection (Wifi) Classification System And Its Predictive Ability Concerning Amputation-Free Survival, Mortality And Major Limb Amputation In A Portuguese Population: A Single Center Experience.

INTRODUCTION: Commonly used chronic limb-threatening ischemia (CLTI) classifications lack granularity and detail to precisely stratify patients according to risk of limb loss, expected revascularization benefit and mortality. The aim of this study is to evaluate in a Portuguese population the prognostic value of an updated CLTI classification based on Wound, Ischemia, and foot Infection (WIfI) proposed by the Society for Vascular Surgery. MATERIALS AND METHODS: Single-center retrospective evaluation of prospectively collected data of consecutive patients with CLTI submitted to lower limb revascularization from January to December of 2017. All consecutive patients with chronic peripheral artery disease with ischemic rest pain or tissue loss were included. The exclusion criteria were patients with intermittent claudication, vascular trauma, acute ischemia, non-atherosclerotic arterial disease and isolated iliac intervention. The primary end-point was major limb amputation, mortality and amputation-free survival (AFS) at 30 days, 1 year and 2 year follow-up. Secondary end-points were minor amputation, wound healing time (WHT) and rate (WHR). RESULTS: A total of 111 patients with CLTI were submitted to infra-inguinal revascularization: 91 endovascular and 20 open surgery. After categorizing them according to the WIfI: 20 had stage 1 (18.52%), 29 stage 2 (26.85%), 38 stage 3 (35.19%) and 21 stage 4 (19.44%). Overall mortality rate was 1.8%, 17% and 22.3% at 30 days, 1 year and 2 years follow-up. Major amputation rate was 0.9%, 2.7% and 2.7% at 30 days, 1 year and 2 years follow-up. AFS rate was 97.3%, 82.1%, and 76.8% at 30 days, 1 year, 2 years follow-up. In multi-variable analysis, higher WIfI score was the only predictive factor for mortality and AFS. WIfI 3 and 4 were also associated with increased risk of non-healing ulcer. CONCLUSION: This study proved the prognostic value of the WIfI classification in a Portuguese population by showing an association between higher scores and increased mortality, lower AFS and non-healing ulcer.

Optimizing the management of thyroid specimens to efficiently generate whole slide images for diagnosis.

Transition from optical to digital observation requires an additional procedure in the pathology laboratory, the scanning of glass slides, leading to increased time and digital archive consumption. Thyroid surgical samples often carry the need to collect several tissue fragments that generate many slides to be scanned. This study evaluated the impact of using different inking colours for the surgical margin, section thickness, and glass slide type, in the consumption of time and archive. The series comprehended 40 nodules from 30 patients, including 34 benign nodules in follicular nodular disease, 1 NIFTP, and 5 papillary carcinomas. In 12 nodules, the dominant pattern was microfollicular/solid and in 28 it was macrofollicular. Scanning times/mm2 were longer in red-inked fragments in comparison to green (p = 0.04) and black ones (p = 0.024), and in blue-inked in comparison to green ones (p = 0.043). File sizes/mm2 were larger in red-inked fragments in comparison to green (p = 0.008) and black ones (p = 0.002). The dominant pattern microfollicular/solid was associated with bigger file size/mm2 in comparison with the macrofollicular one (p < 0.001). All scanner outputs increase significantly with the thickness of the section. All scanning outputs increase with the usage of adhesive glass slides in comparison to non-adhesive ones. Small interventions in thyroid sample management that can help optimizing the digital workflow include to prefer black and green inking colours for the surgical margins and 2 µm section in non-adhesive glass slides for increased efficiency.

How predicted temperature and salinity changes will modulate the impacts induced by terbium in bivalves?

The threat of climate change, which includes shifts in salinity and temperature, has generated a global concern for marine organisms. These changes directly impact them and may alter their susceptibility to contaminants, such as terbium (Tb), found in electronic waste. This study assessed how decreased and increased salinity, as well as increased temperature, modulates Tb effects in Mytilus galloprovincialis mussels. After an exposure period of 28 days, Tb bioaccumulation and biochemical changes were evaluated. Results indicated no significant modulation of salinity and temperature on Tb accumulation, suggesting detoxification mechanisms and adaptations. Further analysis showed that Tb exposure alone caused antioxidant inhibition and neurotoxicity. When exposed to decreased salinity, these Tb-exposed organisms activated defense mechanisms, a response indicative of osmotic stress. Moreover, increased salinity also led to increased oxidative stress and metabolic activity in Tb-exposed organisms. Additionally, Tb-exposed organisms responded to elevated temperature with altered biochemical activities indicative of damage and stress response. Such responses suggested that Tb effects were masked by osmotic and heat stress. This study provides valuable insights into the interactions between temperature, salinity, and contaminants such as Tb, impacting marine organisms. Understanding these relationships is crucial for mitigating climate change and electronic waste effects on marine ecosystems.

From the cellular to tissue alterations induced by two rare earth elements in the mussel species Mytilus galloprovincialis: Comparison between exposure and recovery periods.

The global effort to achieve carbon neutrality has led to an increased demand for renewable energy technologies and their raw materials, namely rare earth elements (REEs). These elements possess unique properties and are used in various applications. However, the increased use of REE-based technologies has resulted in higher amounts of electronic waste, leading to elevated REEs concentrations found in the aquatic environment, with poorly understood threats to wildlife. Praseodymium (Pr) and europium (Eu) are two REEs that, despite their potential environmental risks, have almost unknown effects on aquatic organisms. Therefore, the present study aimed to assess the impacts of different concentrations of Pr and Eu (0, 10, 20, 40, and 80 µg/L) in the mussel species Mytilus galloprovincialis, as well as their ability to recover from exposure to the highest concentration. Mussels accumulated both elements in a dose-dependent manner, with the accumulation of Pr being higher. Accompanying the increase of metabolism, mussels exposed to Pr not only enhanced the activity of the antioxidant enzymes superoxide dismutase (up to 40 µg/L) and glutathione reductase (at 80 µg/L) but also the activity of the biotransformation enzymes carboxylesterases (CbE's) and glutathione S-transferases (GSTs) (at 80 µg/L). Nevertheless, these defence mechanisms were not sufficient to prevent cellular damage. All the Eu concentrations induced cellular damage, despite an increase in the activity of biotransformation enzymes (CbE's and GSTs) in mussel tissue. According to the histopathology assessment, mussels were not able to recover after exposure to both elements and lower concentrations induced higher injuries in digestive tubules. This study highlights that exposure to Pr and Eu had adverse effects on M. galloprovincialis, even at the lowest tested concentration, which may eventually impact mussels' growth, reproductive capacity, and survival.

Yttrium effects on the Mediterranean mussel under a scenario of salinity shifts and increased temperature.

Climate change (CC) induces significant worldwide alterations in salinity and temperature, impacting ecosystems and their services. Marine organisms, susceptible to these changes, may experience modified vulnerability to anthropogenic contaminants, including rare-earth elements (REEs) such as yttrium (Y) derived from electronic waste. This study investigated the influence of temperature and salinity changes on the impacts of Y in Mytilus galloprovincialis mussels. Organisms were subjected to Y (0 and 10 µg/L) for 28 days under three salinity scenarios (20, 30 (control), and 40, at a control temperature of 17 °C) or to two temperatures (17 and 22 °C, at the control salinity of 30). Under these conditions, Y bioaccumulation and different biomarkers were evaluated. Results showed that salinity and temperature did not affect Y accumulation, indicating effective detoxification mechanisms and physiological adaptations in the exposed organisms. However, in Y-exposed mussels effects were intensified under decreased salinity, evidenced by increased metabolism, defense enzyme activities, and acetylcholinesterase (AChE) levels. Similar responses occurred under heat stress with enhanced metabolic capacity, AChE activity, and activation of defense mechanisms such as glutathione S-transferases. These defense mechanisms mitigated cellular damage caused by Y, but under the highest temperature and especially lower salinity, Y-exposed mussels exhibited increased oxidative stress and decreased efficiency of activated defense enzymes, resulting in cellular damage compared to their uncontaminated counterpart. The present study sheds light on the effects that interactions between temperature, salinity, and the presence of emerging contaminants like REEs may have on marine organisms. Such assessments are crucial for developing effective strategies to mitigate the impacts of CC and protect the long-term health and resilience of marine ecosystems.

Intervenções de enfermagem para gerir a dor na canulação da fístula arteriovenosa ­ scoping review / Nursing interventions to manage pain in arteriovenous fistula cannulation - scoping review

O presente relatório de estágio, foi elaborado no âmbito do Mestrado em Enfermagem Médico-Cirúrgica da Escola Superior de Saúde do Instituto Politécnico de Bragança, alusivo ao período entre setembro de 2020 e abril de 2021, realizado em três serviços distintos ­ Serviço de Urgência Médico-Cirúrgica, Unidade de Cuidados Intensivos e Bloco Operatório ­ que proporcionou o aprimoramento de competências clínicas e de pesquisa como enfermeiro especialista. A pesquisa pelo progresso no conhecimento demanda uma prática fundamentada nas evidências mais recentes, orientada para resultados sensíveis aos cuidados de enfermagem. O enfermeiro especialista assume um papel central como líder em projetos de formação, consultoria e investigação, conforme o regulamento da Ordem dos Enfermeiros (OE n.º 429/2018 de julho, p.19360). A atuação do Enfermeiro Especialista em Enfermagem Médico-Cirúrgica perante pacientes em estado crítico demanda conhecimentos precisos e competências específicas. O estágio concentrou-se no desenvolvimento de competências comuns e específicas em enfermagem Médico-Cirúrgica na área da pessoa em situação critica, desde a gestão de doenças críticas até a atuação em emergências, conforme os regulamentos nº 140/2019 e nº429/2018 da OE. O estágio realizado na Unidade Local de Saúde do Litoral Alentejano, abrangeu os serviços de Urgência Médico-Cirúrgica, Bloco Operatório e Unidade de Cuidados Intensivos. Os objetivos gerais incluíram consolidar e analisar competências adquiridas, identificar situações e dificuldades na prática clínica, elaborar uma reflexão aprofundada sobre as práticas nos diferentes serviços e contribuir para a aquisição do Grau de Mestre em Enfermagem Médico-Cirúrgica. Durante o estágio foi incentivado a prática baseada na evidencia e, por esse mesmo motivo, foi realizado um artigo científico com o tema - "Intervenções de Enfermagem para Gerir a Dor na Canulação da Fistula Arteriovenosa ­ Scoping Review" - submetido à Revista Referência. O relatório em conjunto com o artigo científico, representa a síntese do percurso educacional e profissional, visando aprimorar competências práticas e contribuir para o avanço do conhecimento.

Pressure dynamics of the esophagogastric junction at rest and during inspiratory maneuvers after Nissen fundoplication.

Low sphincter pressure and inability of the crural diaphragm to elevate it at the esophagogastric junction are important pathophysiological mechanisms of gastroesophageal reflux disease (GERD). The object of this study was to depict how Nissen fundoplication changed the resting and inspiratory pressures of the anti-reflux barrier. We selected 14 patients (eight males; mean age 42.7 years; mean body mass index 27.8) for surgery. They answered symptoms questionnaires and underwent high-resolution manometry (HRM) before and 6 months after Nissen fundoplication. We used a standard manometric protocol (resting and liquid swallows) and assessment of esophagogastric junction (EGJ) pressure metrics during standardized forced inspiratory maneuvers against increasing loads (Threshold Maneuvers). We used the Wilcoxon test for comparison of pre and postoperative data. After fundoplication, heartburn and regurgitation scores diminished remarkably (from 4.5 and 2, respectively, to zero; P = 0.002 and P = 0.0005, respective medians). Also, the median expiratory EGJ pressure had a significant increase from 8.1 to 18.1 mmHg (P = 0.002), while mean respiratory pressure and EGJ contractility integral (EGJ-CI) increased without statistical significance (P = 0.064 and P = 0.06, respectively). Axial EGJ displacement was lower after fundoplication. The EGJ relaxation pressure (P = 0.001), the mean distal esophageal intrabolus pressure (P = 0.01) and the distal latency (P = 0.017) increased after fundoplication. There was a reduction in the contraction front velocity (P = 0.043). During evaluation with standardized inspiratory maneuvers, the inspiratory EGJ pressures (under loads of 12, 24, 36 and 48 cmH2O) were lower after surgery for all loads (median for load 12 cmH2O: 145.6 vs. 102.7 mmHg; P = 0.004). Fundoplication and hiatal closure increased the expiratory EGJ pressure and promoted a great GERD symptom relief. The surgery seemed to overcompensate a reduced EGJ mobility and inspiratory pressure.

Loss of RAS Mutations in Liquid Biopsies of Patients With Multi-Treated Metastatic Colorectal Cancer.

BACKGROUND: Liquid biopsy (LB) is a non-invasive tool to evaluate the heterogeneity of tumors. Since RAS mutations (RAS-mut) play a major role in resistance to antiepidermal growth factor receptor inhibitors (EGFR) monoclonal antibodies (Mabs), serial monitoring of RAS-mut with LB may be useful to guide treatment. The main aim of this study was to evaluate the prognostic value of the loss of RAS-mut (NeoRAS-wt) in LB, during the treatment of metastatic colorectal cancer (mCRC). METHODS: A retrospective study was conducted on patients with mCRC between January 2018 and December 2021. RAS-mut were examined in tissue biopsy, at mCRC diagnosis, and with LB, during treatment. RESULTS: Thirty-nine patients with RAS-mut mCRC were studied. LB was performed after a median of 3 lines (0-7) of systemic treatment including anti-vascular endothelial growth factor (anti-VEGF) Mabs. NeoRAS-wt was detected in 13 patients (33.3%); 9 (69.2%) of them received further treatment with anti-EGFR Mabs with a disease control rate of 44.4%. Median overall survival (OS), from the date of LB testing, was 20 months in the NeoRAS-wt group and 9 months in the persistent RAS-mut group (log-rank 2.985; P = .08), with a 12-month OS of 84.6% and 57.7%, respectively. NeoRAS-wt was identified as a predictor of survival (HR = 0.29; P = .007), with an 11-month improvement in median OS and a 71% decrease in risk of death, in heavily pretreated patients. CONCLUSIONS: In conclusion, monitoring clonal evolution in mCRC by LB may provide an additional treatment line for patients with NeoRAS-wt in advanced disease.

Laryngeal Dystonia, Dystonic Tremor and Vocal Tremor: Three Different Entities.

OBJECTIVE: The main objective of this study was to compare the demographic and clinical characteristics of patients with laryngeal dystonia (LD), dystonic tremor (DT), and vocal tremor (VT). STUDY DESIGN: This was a retrospective longitudinal study. METHODS: Data analysis from every patient diagnosed with LD, DT, or VT from January 1, 2010, to September 30, 2022, at a tertiary hospital center. Differential diagnosis between these entities was clinical (clinical history, voice assessment, and endoscopy) and confirmed by laryngeal electromyography. RESULTS: A total of 87 patients were included in this study: 50 patients with LD, 23 with DT, and 14 with VT. Age at diagnosis was significantly lower in patients with LD, with a mean age of 56.2 years when compared to DT (67.6 years; P = 0.002) and VT (70.5 years; P = 0.009). Furthermore, VT had a higher female prevalence (92.9%) when compared with LD (52%; P = 0.011). LD was mainly adductor, with only two patients diagnosed with abductor LD, and DT was adductor in every case. Tremor direction in patients with VT was horizontal in 50% and mixed (horizontal + vertical) in 50%, while in DT was mixed in 65.2% and horizontal in 34.8%. LD was more commonly an isolated laryngeal movement disorder (78%) when compared to DT (47.8%; P = 0.015) or VT (28.5%; P < 0.001), which were more often secondary to generalized neurological disorders. There were no differences between groups on Voice Handicap Index-10, self-reported grade of dysphonia on a visual analogic scale (0-10), maximum phonation time, and G, R, B, A, and I in the GRBAS-I scale at diagnosis (P > 0.05). S was significantly higher in LD when compared to VT (P < 0.001) and nonsignificantly higher than in DT (P = 0.075). CONCLUSIONS: LD, DT, and VT seem to be different entities with different demographics and clinical characteristics.

Recurrent Appendicitis in Children: The Impact of a Poorly Known Disease.

Chronic and recurrent appendicitis is rare in pediatric patients and can be easily misdiagnosed due to its unusual presentation and low incidence rate. We present the case of an 11-year-old male with recurrent right lower quadrant (RLQ) pain persisting for 19 months. The patient experienced pain flare-ups accompanied by paleness and gait limp, without fever or other symptoms. Despite extensive medical examinations, including imaging and endoscopy, a definitive diagnosis remained elusive. As serial abdominal ultrasounds reported an appendix at the upper limit of the normal caliber and symptoms persisted despite medical therapy, a diagnostic laparoscopy was performed, revealing a congested ileocecal appendix with erosions and granulocytic inflammatory infiltrate, consistent with appendicitis. Post-appendectomy, the patient's symptoms resolved, significantly improving his quality of life (QoL), as evidenced by the DISABKIDS Chronic Generic Module (DCGM). This case underscores the challenges in diagnosing chronic and recurrent appendicitis, emphasizing the need for improved awareness, case definitions, and research to better understand and manage these conditions. Moreover, the report highlights the substantial impact of such conditions on patients' physical, social, and psychological well-being using the only health-related QoL instrument developed across cultures for children with chronic diseases: the DCGM.

Anopheles gambiae on remote islands in the Indian Ocean: origins and prospects for malaria elimination by genetic modification of extant populations.

The mosquito Anopheles gambiae s.s. is a primary malaria vector throughout sub-Saharan Africa including the islands of the Comoros archipelago (Anjouan, Grande Comore, Mayotte and Mohéli). These islands are located at the northern end of the Mozambique Channel in eastern Africa. Previous studies have shown a relatively high degree of genetic isolation between the Comoros islands and mainland populations of A. gambiae, but the origin of the island populations remains unclear. Here, we analyzed phylogenetic relationships among island and mainland populations using complete mitochondrial genome sequences of individual A. gambiae specimens. This work augments earlier studies based on analysis of the nuclear genome. We investigated the source population of A. gambiae for each island, estimated the number of introductions, when they occurred and explored evidence for contemporary gene flow between island and mainland populations. These studies are relevant to understanding historical patterns in the dispersal of this important malaria vector and provide information critical to assessing their potential for the exploration of genetic-based vector control methods to eliminate this disease. Phylogenetic analysis and haplotype networks were constructed from mitogenome sequences of 258 A. gambiae from the four islands. In addition, 112 individuals from seven countries across sub-Saharan Africa and Madagascar were included to identify potential source populations. Our results suggest that introduction events of A. gambiae into the Comoros archipelago were rare and recent events and support earlier claims that gene flow between the mainland and these islands is limited. This study is concordant with earlier work suggesting the suitability of these oceanic islands as appropriate sites for conducting field trial releases of genetically engineered mosquitoes (GEMs).

Exploring Environmental Settings to Improve the Printability of Paroxetine-Loaded Filaments by Fused Deposition Modelling.

The successful integration of hot-melt extrusion (HME) and fused deposition modelling (FDM) depends on a better understanding of the impact of environmental conditions on the printability of formulations, since they significantly affect the properties of the raw materials, whose control is crucial to enable three-dimensional printing (3DP). Hence, the objective of this work was to investigate the correlation between the environmental settings and the properties of paroxetine (PRX)-loaded filaments, previously produced by HME, which affect printability by FDM. The influence of different drying methods of the physical mixtures (PMs) and HME-filaments (FILs) on the quality and printability of these products was also assessed. The printability of FILs was evaluated in terms of the water content, and the mechanical and thermal properties of the products. Stability studies and physicochemical, thermal, and in vitro dissolution tests were carried out on the 3D-printed tablets. Stability studies demonstrated the high ductility of the PRX loaded FILs, especially under high humidity conditions. Under low humidity storage conditions (11% RH), the FILs became stiffer and were successfully used to feed the FDM printer. Water removal was slow when carried out passively in a controlled atmosphere (desiccator) or accelerated by using active drying methods (heat or microwave). Pre-drying of the PRX/excipients and/or PMs did not show any positive effect on the printability of the FIL. On the contrary, dry heat and, preferably, microwave mediated drying processes were shown to reduce the holding time required for successful FDM printing, enabling on-demand production at the point of care.