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To evaluate the association of dry eye disease (DED) subtypes (aqueous deficient dry eye, ADDE and evaporative dry eye, EDE) and the presence of rheumatoid arthritis (RA) in patients. 260 volunteer DED participants were recruited for an observational cross-sectional study based on the Tear Film Ocular Society Dry Eye Workshop II criteria, which included tear film osmolarity, fluorescence break-up time, and ocular surface damage assessment. Participants were recruited using QR linked to designated mobile forms to obtain symptomatology status, demographics, and RA diagnosis by their medical doctor. Tear meniscus and lipid layer were also evaluated to differentiate between ADDE, EDE, or mixed dry eye in addition to the DED diagnostic criteria. Participants with mixed dry eye were excluded from the analysis to avoid bias. After initial recruitment, 149 eligible participants with an ADDE or EDE diagnosis were included in the final analysis, where 12,1% have an RA diagnosis. The ADDE group had a higher likelihood of having RA (OR = 4.69, 95 %CI = 1.46–15.01) than the EDE group. Additionally, the number of participants with RA in the ADDE group was statistically higher than those in the EDE group (all p = 0.006). Furthermore, a correlation was obtained between RA and a diagnosis of ADDE (p = 0.005). There was a significant association between ADDE and the presence of RA in patients and the association was more likely compared to those with EDE. This finding underscores the need for specific diagnostic and management strategies for RA patients presenting with DED. [ABSTRACT FROM AUTHOR]

Endoscopic Submucosal Dissection (ESD) has been reported as a feasible and effective treatment for Rectal Neuroendocrine Tumours (R-NETs). However, most of the experience on the topic comes from retrospective tertiary centre from Eastern Asia. Data on ESD for R-NETs in Western centres are lacking. This is a retrospective study, including patients who underwent endoscopic resection of R-NETS by ESD between 2015 and 2020 in Western Centres. Important clinical variables such as demographic, size of R-NETs, histological type, presence of lymphovascular invasion or distant metastasis, completeness of the endoscopic resection, recurrence, and procedure related complications were recorded. 40 ESD procedure on R-NETs from 39 patients from 8 centres were included. Mean R-NETs size was 10.3 mm (SD 4.01). Endoscopic en-bloc resection was achieved in 39/40 ESD (97.5 %), R0 margin resection was obtained in 87.5 % (35/40) of the procedures, one patient was referred to surgery for lymphovascular invasion, two procedures (5 %) reported significant episodes of bleeding, whereas a perforation occurred in one case (1/40, 2.5 %) managed endoscopically. Recurrence occurred in 1 patient (2.5 %). ESD is an effective and safe treatment for R-NETs in western centres. [ABSTRACT FROM AUTHOR]

Previous isolated reports have hypothesized that chewing coca leaves, a pre-Columbian tradition found in certain regions of South America, may be associated with the development of oral squamous cell carcinoma (OSCC). Coca chewing (CC) is a habit that shares many characteristics with the well-known practice of betel chewing observed in Asia. The aim of this study is to analyze the association between CC and OSCC among patients who attended the Señor del Milagro Hospital in Salta, Argentina. A case-control study was conducted from 2013 to 2018. For each case of OSCC, three healthy control patients were included. Odds ratios were calculated to compare demographics, concurrent oral conditions, and other classical risk factors for OSCC. A total of 62 cases and 180 controls were included, adjusted for sex and age. OSCC was significantly associated with tobacco use (27.4% vs 9.4%, P =.001), CC (62.9% vs 32.2%, P <.001), and poor oral condition (81.1% vs 67.7%, P =.02). In the multivariate analysis, smoking (OR = 2.77, 95% CI 1.23-6.25, P =.0139), CC (OR = 2.98, 95% CI 1.58-5.63, P =.0007), and poor oral condition (OR = 3.1, 95% CI 1.62-5.85, P =.0006) remained independently associated with OSCC development. Chewing coca leaves could be considered a risk factor for oral cancer in a subset of Argentinean patients. Further studies are necessary to validate our findings and to elucidate the underlying pathways linking this habit to oral carcinogenesis. [ABSTRACT FROM AUTHOR]

Transvenous laser lead extraction poses a risk of major complications (0.19%–1.8%), notably injury to the superior vena cava (SVC) in 0.19% to 0.96% of cases. Various factors contribute to SVC injury, which can be categorized as patient-related (such as female gender, low body mass index, diabetes, renal problems, anemia, and reduced ejection fraction), device-related (including the number, dwell time, and type of leads), or procedural-related (such as reason for extraction, venous obstructions, and bilateral lead placements). [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is associated with higher cardiovascular and metabolic risks, as well as with psychosocial disorders. Data regarding quality of life (QoL) in patients with MetS, point towards a significative association between MetS and a worse QoL. It remains unclear whether MetS components and non-alcoholic fatty liver disease (NAFLD) are associated with QoL in these individuals. We aimed to evaluate the association between QoL of patients with MetS and prespecified metabolic parameters (anthropometric, lipidic and glucose profiles), the risk of hepatic steatosis and fibrosis, and hepatic elastography parameters. Cross-sectional study including patients from microDHNA cohort. This cohort includes patients diagnosed with MetS, 18 to 75 years old, followed in our tertiary center. The evaluation included anamnesis, physical examination, a QoL questionnaire (Short-Form Health Survey, SF-36), blood sampling and hepatic elastography. We used ordered logistic regression models adjusted to sex, age and body mass index to evaluate the associations between the QoL domains evaluated by SF-36 and the prespecified parameters. We included a total of 65 participants with MetS, with 54% being female and the mean age 61.9 ± 9.6 years old. A worse metabolic profile, specifically higher waist circumference, lower HDL, higher triglycerides, and more severe hepatic steatosis, were associated with worse QoL scores in several domains. We found no significant association of hepatic fibrosis with QoL. Our data suggests that there is a link between a worse metabolic profile (specifically poorer lipidic profile and presence of hepatic steatosis) and a worse QoL in patients with MetS. • There is scarce data on quality of life in MetS, regarding metabolic parameters. • We showed that higher waist circumference associated with worse QoL. • Lower HDL and higher triglycerides associated with worse QoL. • More severe hepatic steatosis but not fibrosis associated with worse QoL. [ABSTRACT FROM AUTHOR]

• 1030 patients with hypertensive disorders of pregnancy were enrolled in a remote patient monitoring program for hypertension (RPM HTN) and 937 were compared to a matched historical cohort. • Patients in the program were more likely to have their blood pressures measured postpartum after hospital discharge, more likely to have that blood pressure be normal, and were more likely to be evaluated by an obstetric clinician within 3 and 8 weeks and a primary care clinician within 1–3 months after delivery. • RPM HTN led to improved standardized management, better postpartum blood pressure control, and improved linkages to obstetric and primary care postpartum. To determine the effect of a remote patient monitoring program for hypertension (RPM HTN) in patients diagnosed with hypertensive disorders of pregnancy. We used a matched retrospective cohort design to evaluate differences in obstetric and perinatal outcomes using data from electronic medical records. Patients enrolled in RPM HTN between November 1, 2019, and October 31, 2021, who delivered a pregnancy at ≥20 weeks gestation were compared to a cohort of patients matched by age, race, HTN and diabetes status, who delivered in the 48-month period before implementation of RPM HTN. 1030 patients were enrolled in RPM HTN and 937 were matched to historical controls. Five hundred and seventeen (50.2 %) were enrolled in the antepartum period and 513 (49.8 %) were enrolled postpartum. Patients in the RPM HTN cohort were more likely to have a post-hospital discharge blood pressure (BP) measured within the first 20 days after delivery (RR 1.56, 95 % CI: 1.47–1.65: p < 0.01) and were more likely to have that BP be normal (RR 1.43, 95 % CI: 1.31–1.55: p = 0.05). They were also more likely to be taking antihypertensives postpartum (RR 1.27, 95 % CI: 1.15–1.40; p < 0.01) and to be evaluated by an obstetric clinician within 20 days of delivery (RR 1.50, 95 % CI 1.42–1.58; p < 0.01). A remote HTN monitoring program for 937 obstetric patients was associated with improved BP monitoring, better postpartum BP control, and improved linkages to clinician care after delivery, when compared to historical controls. [ABSTRACT FROM AUTHOR]

Despite accelerated research in small intestinal bacterial overgrowth (SIBO), questions remain regarding optimal diagnostic approaches and definitions. Here, we aim to define SIBO using small bowel culture and sequencing, identifying specific contributory microbes, in the context of gastrointestinal symptoms. Subjects undergoing esophagogastroduodenoscopy (without colonoscopy) were recruited and completed symptom severity questionnaires. Duodenal aspirates were plated on MacConkey and blood agar. Aspirate DNA was analyzed by 16S ribosomal RNA and shotgun sequencing. Microbial network connectivity for different SIBO thresholds and predicted microbial metabolic functions were also assessed. A total of 385 subjects with <103 colony forming units (CFU)/mL on MacConkey agar and 98 subjects with ≥103 CFU/mL, including ≥103 to <105 CFU/mL (N = 66) and ≥105 CFU/mL (N = 32), were identified. Duodenal microbial α-diversity progressively decreased, and relative abundance of Escherichia/Shigella and Klebsiella increased, in subjects with ≥103 to <105 CFU/mL and ≥105 CFU/mL. Microbial network connectivity also progressively decreased in these subjects, driven by the increased relative abundance of Escherichia (P <.0001) and Klebsiella (P =.0018). Microbial metabolic pathways for carbohydrate fermentation, hydrogen production, and hydrogen sulfide production were enhanced in subjects with ≥103 CFU/mL and correlated with symptoms. Shotgun sequencing (N = 38) identified 2 main Escherichia coli strains and 2 Klebsiella species representing 40.24% of all duodenal bacteria in subjects with ≥103 CFU/mL. Our findings confirm ≥103 CFU/mL is the optimal SIBO threshold, associated with gastrointestinal symptoms, significantly decreased microbial diversity, and network disruption. Microbial hydrogen- and hydrogen sulfide–related pathways were enhanced in SIBO subjects, supporting past studies. Remarkably few specific E coli and Klebsiella strains/species appear to dominate the microbiome in SIBO, and correlate with abdominal pain, diarrhea, and bloating severities. [Display omitted] [ABSTRACT FROM AUTHOR]

Approximately 80% of global trade is transported by sea, so ports must adjust to sustain competitiveness in the market. For this, ports are making a transition from traditional ports to digital ports, incorporating technology, giving rise to the concept of "Smart Port". Considering the relevance and novelty of this topic, that researchers are trying to investigate, the main objective of this work is to contribute to it by answering the question: "What is known about smart ports around the world?", with a focus on the impacts of smart ports on sustainable development goals (SDG) 8 (decent work and economic growth), 9 (industry, innovation, and infrastructure) and 11 (sustainable cities and communities). Thus, a Google search was carried out on the different websites of port authorities and maritime data solutions, to perform a benchmarking of what is already a reality regarding existing smart ports. Therefore, this study has contributions both at the theoretical level, by identifying good practices in terms of technology and initiatives, to bring knowledge to the academia about what already exists in smart ports, and at the practical level, by helping other seaports to advance in the digital state and become more intelligent, providing ideas for the implementation of initiatives that allow the modernization of ports (contributing to sustainability in different dimensions). [ABSTRACT FROM AUTHOR]

Septic arthritis of the temporomandibular joint (SATMJ) is an uncommon bacterial or fungal infection of the joint space. A 68-year-old man with underlying diabetes mellitus and a history of liver transplant, who was on immunosuppressants, presented to the oral and maxillofacial surgery department of the authors´ institution in Portugal. His main symptoms were arthralgia in the right temporomandibular joint, malocclusion, pre-auricular swelling and erythema. After clinical, laboratory, and imaging evaluations, diagnoses of chronic suppurative otitis media and SATMJ were made. The patient was managed with arthroscopy of the right temporomandibular joint, which allowed joint fluid collection for microbiological examination, lavage, and biopsy. The biopsy sample was positive for Pseudomonas aeruginosa. After surgery, targeted intravenous antibiotic treatment (amikacin) was given for 30 days. No recurrence of any complaints was reported after 12 months of follow-up. [ABSTRACT FROM AUTHOR]

Cardiac amyloidosis is a restrictive cardiomyopathy for which diuretics are frequently used, but vasodilators have classically been relatively contraindicated due to side effects of hypotension. In the setting of decompensated heart failure, this may not be the case. We report a man with advanced cardiac amyloidosis who presented to the hospital with decompensated heart failure, in part, due to elevated systemic vascular resistance. Through the use of invasive hemodynamic testing, we were able to demonstrate an increase in cardiac output in response to a nitroprusside challenge. In turn, the patient had an improvement in his symptoms and was sent home on afterload reducing medications. This discerns a subpopulation of cardiac amyloidosis patients in decompensated heart failure who benefit from medications that reduce systemic vascular resistance, and can benefit from hemodynamic testing, especially when diuretics fail to control symptoms. Medications that cause peripheral vasodilation are standard therapy for patients with reduced ejection fraction, however, they are seldom used for patients with cardiac amyloidosis due to adverse effects. In some cases, there may be value in using hemodynamic measurements in patients with advanced cardiac amyloidosis to guide management as some patients may have hemodynamics that resemble those of systolic heart failure. This may offer a novel approach to symptomatic treatment of advanced cardiac amyloidosis. [ABSTRACT FROM AUTHOR]

Symptomatic non-obstructive hypertrophic cardiomyopathy (HCM) presents significant diagnostic and therapeutic challenges. While myosin inhibition has shown benefits in obstructive HCM, its efficacy in non-obstructive HCM remains unclear. Both patient groups share a similar risk for HCM-related mortality, yet current therapeutic approaches for non-obstructive HCM are limited and primarily focus on symptom management rather than targeting underlying molecular mechanisms. The R92L mutation in cardiac troponin T, a common cause of HCM, leads to increased power of contraction that is energetically costly, resulting in an imbalance of myocardial energetics. It is well established that the phosphocreatine (PCr) to ATP ratio is decreased in HCM, and analysis of human myectomy samples shows associated severe structural mitochondrial damage. This energetic impairment contributes to diastolic dysfunction, and limited data suggest that metabolic interventions may offer therapeutic benefits in non-obstructive HCM. CK-271, a specific cardiac myosin inhibitor related to aficamten, has demonstrated potential in modulating myocardial contractility and improving cardiac function. This study investigates the efficacy of CK-271 in enhancing myocardial energetics, reducing hypertrophy, and improving diastolic function and exercise tolerance in a mouse model of non-obstructive HCM with the R92L troponin T mutation. We hypothesize that CK-271, a small molecule myosin inhibitor, will improve myocardial energetics, reduce cardiac hypertrophy, and enhance diastolic function, thereby improving exercise tolerance in a mouse model of non-obstructive hypertrophic cardiomyopathy (HCM) with the R92L troponin T mutation. Adult mice with fully developed hypertrophy due to the troponin R92L mutation were treated with the myosin inhibitor CK-271 in the diet for 16 weeks. Using 31P NMR spectroscopy, cardiac energetics were assessed by measuring the phosphocreatine (PCr) to ATP ratio. In R92L mice, treatment with CK-271 improved cardiac energetics, as evidenced by increased PCr/ATP ratios, which was associated with reduced left ventricular hypertrophy (decreased total wall thickness), decreased contractility, and improved diastolic function (increased E/A ratio and Em). Strikingly, CK-271 treatment also improved exercise tolerance in R92L mice. Our novel study suggests that the structural and functional benefits of myosin inhibition in HCM are, at least in part, due to improved cardiac energetics. This provides evidence supporting the conduct of clinical trials with myosin inhibition and/or metabolic modulation in non-obstructive HCM. [ABSTRACT FROM AUTHOR]

In recent decades, the professionalization of pharmacy has been debated worldwide. With the advent of industrialization, pharmacist autonomy has weakened, especially in the retail pharmacy market. Manegers and mentors of pharmacy chains serve as links between the profession and drug users. This study sought to understand the perceptions of retail pharmacy stakeholders regarding pharmacist autonomy and how to improve it, and to reflect on theories of professionalism. 19 semi-structured interviews were conducted. The interviews were transcribed and analyzed through analyst triangulation and categorical content analysis, using the ATLAS.ti software. Interviews were conducted with nine mentors and ten managers in retail medicine. They reported aspects related to managerial and technical autonomy regulated by law, and strategies for enhancing professional autonomy in retail pharmacy. Autonomy was considered limited by pharmacists' dependence on employability and self-devaluation; and market control exposed the weaknesses in pharmaceutical professionalism. Entrepreneurship and ownership attitude strategies were feasible only in a retail micro-political context. The retail medicine continues to have business model centered on the product and controlling the pharmaceutical practice model. To ensure autonomy and professional strengthening, it is necessary that pharmacy recognizes itself as a clinical profession and develops a stable professional identity. [ABSTRACT FROM AUTHOR]

The aim of this review was to analyze the evidence of whey protein supplementation on body weight, fat mass, lean mass and glycemic parameters in subjects with overweight or type 2 diabetes mellitus (T2DM) undergoing calorie restriction or with ad libitum intake. Overweight and obesity are considered risk factors for the development of chronic noncommunicable diseases such as T2DM. Calorie restriction is a dietary therapy that reduces weight and fat mass, promotes the improvement of glycemic parameters, and decreases muscle mass. The maintenance of muscle mass during weight loss is necessary in view of its implication in preventing chronic diseases and improving functional capacity and quality of life. The effects of increased protein consumption on attenuating muscle loss and reducing body fat during calorie restriction or ad libitum intake in overweight individuals are discussed. Some studies have demonstrated the positive effects of whey protein supplementation on improving satiety and postprandial glycemic control in short term; however, it remains unclear whether long-term whey protein supplementation can positively affect glycemic parameters. Although whey protein is considered to have a high nutritional quality, its effects in the treatment of overweight, obese individuals and those with T2DM undergoing calorie restriction or ad libitum intake are still inconclusive. • Protein consumption has been shown to attenuate muscle loss. • Whey protein may optimize body fat loss during calorie restriction or in ad libitum intake. • Whey protein supplementation is considered to be an important factor in improving satiety during the weight loss process. • Whey protein supplementation improves insulin resistance. [ABSTRACT FROM AUTHOR]

Oculodentodigital dysplasia (ODDD; MIM #164200), a rare genetic disorder characterized by abnormal craniofacial, dental, ocular, and digital features, is caused by mutations in GJA1 (gap junction alpha-1) gene and inherited in an autosomal dominant pattern. However, an autosomal recessive pattern is also reported. Here we described 2 families with members affected by ODDD. In the first family, the c.752G>C (p.S251T) and c.848C>T (p.P283L) heterozygous missense mutations and the c.825C>T (p.T275T) silent mutation were identified in the proband, which showed mild ODDD phenotypes, and in his mother, which displayed hemolytic anemia and thrombocytopenia. In the second family, the patients displayed typical features of ODDD, and Sanger sequencing identified a novel homozygous c.604C>T (p.R202C) missense mutation, whereas the parents carried the mutation. Together, these findings suggest that homozygous mutation in GJA1 induces a more severe ODDD phenotype, though interfamilial phenotype variability was observed, whereas compound heterozygous mutations in GJA1 cause a mild phenotype. Submission declaration: This article has not been previously published; it is not under consideration for publication elsewhere. Its publication has been approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out. If accepted, it will not be published elsewhere including digitally in the same form, in English or in any other language, without the written consent of the copyright holder. [ABSTRACT FROM AUTHOR]

Malaria is among the tropical diseases that cause the most deaths in Africa. Around 500,000 malaria deaths are reported yearly among African children under the age of five. Chloroquine (CQ) is a low-cost antimalarial used worldwide for the treatment of Plasmodium vivax malaria. Due to resistance mechanisms, CQ is no longer effective against most malaria cases caused by P. falciparum. The World Health Organization recommends artemisinin combination therapies for P. falciparum malaria, but resistance is emerging in Southeast Asia and some parts of Africa. Therefore, new medicines for treating malaria are urgently needed. Previously, our group identified the 4-aminoquinoline DAQ , a CQ analog containing an acetylenic bond in its side chain, which overcomes CQ resistance in K1 P. falciparum strains. In this work, the antiplasmodial profile, drug-like properties, and pharmacokinetics of DAQ were further investigated. DAQ showed no cross-resistance against standard CQ -resistant strains (e.g., Dd2, IPC 4912, RF12) nor against P. falciparum and P. vivax isolates from patients in the Brazilian Amazon. Using drug pressure assays, DAQ showed a low propensity to generate resistance. DAQ showed considerable solubility but low metabolic stability. The main metabolite was identified as a mono N -deethylated derivative (DAQ M), which also showed significant inhibitory activity against CQ -resistant P. falciparum strains. Our findings indicated that the presence of a triple bond in CQ -analogues may represent a low-cost opportunity to overcome known mechanisms of resistance in the malaria parasite. [Display omitted] • 4-aminoquinoline antimalarial candidates containing a triple bond did not show in vitro cross-resistance against CQ -resistant strains. • DAQ showed a low propensity to generate resistant mutants in vitro after 90 days of drug pressure. • DAQ was active against Plasmodium falciparum and P. vivax field isolates from Brazilian Amazon. • DAQ M , the main metabolite of DAQ , also potently inhibited both CQ -sensitive and CQ -resistant strains. [ABSTRACT FROM AUTHOR]

This study evaluated effects of watermelon fermentation using different non- Saccharomyces yeast strains (Brettanomyces lambicus , Brettanomyces bruxellensis , and Lachancea thermotolerans) on the chemical profile of the derived wines. A control product was produced using Saccharomyces cerevisiae. Analytical techniques, namely HPLC-DAD-RID and LLE-GC/MS, were used to evaluate sugars, organic acids, alcohols, phenolic compounds, amino acids, and volatile compounds profiles. Fermentation reduced the sugar (glucose and fructose) and amino acid contents and increased alcohol (ethanol and glycerol), organic acids (lactic and acetic acids), phenolics, and volatile compounds. The use of the B. bruxellensis strain resulted in an alcoholic beverage with quality parameters similar to that from S. cerevisiae but with higher concentrations of phenolics (rutin, gallic acid, caftaric acid, and caffeic acid) and important volatile compounds (isoamyl acetate). The watermelon wine had a higher content of bioaccessible phenolic compounds than the must, especially catechin, procyanidin B1, procyanidin B2 and gallic acid, due to their high bioaccessibility (>70%). The yeast type influenced the chemical profile of the beverages. B. bruxellensis is a promising tool to obtain watermelon alcoholic beverage in an industrial scale. [Display omitted] • Nonconventional yeasts displayed suitable fermentation profiles for watermelon wine. • Brettanomyces and Lachancea yeasts exhibited suitable fermentation metabolites. • Fermenting B. bruxellensis produced a wine similar to that produced by S. cerevisiae. • The fermented watermelon had a higher content of bioaccessible phenolics. [ABSTRACT FROM AUTHOR]

Probiotics must survive processing and storage, incorporation into foods, and passage through the gastrointestinal system to have the expected effect on the host's health. Encapsulation is widely used to protect probiotic cultures and it may be impacted by the encapsulating material. This review presents and discusses, for the first time, the utilization of unconventional foods and by-products as encapsulating materials to protect probiotics and their incorporation into food products, highlighting the most used encapsulation methods and probiotics. Animal-derived materials (goat milk, camel milk protein, and silk sericin protein), alternative plant proteins, fruit juices and powders, and food by-products were the main unconventional foods used as encapsulating materials. They provided higher probiotic survival during encapsulation and simulated gastrointestinal conditions (SGIC), thermal processing, salt content, and storage conditions. Lactobacillus and amended genera and Bifidobacterium were the most used probiotics , with prominence for Lactiplantibacillus plantarum and Limosilactobacillus reuteri , while extrusion, spray-drying, and freeze-drying were the most used encapsulation methods. The main factors to be considered are the encapsulating material's chemical composition and concentration, probiotic strain, and process parameters. Dairy products were the main food products incorporated with encapsulated probiotics, resulting in improved probiotic survival during refrigerated storage and/or SGIC, extended shelf life, modulation of the mice microbiota, increased in vitro antidiabetic properties, and suitable acceptance by consumers. Further studies could evaluate probiotic yeasts, different food by-products as encapsulating materials, and less expensive encapsulation methods. Encapsulated probiotics using unconventional foods during food processing are underexplored. • First review on using unconventional foods and by-products to protect probiotics. • Alternative plant proteins and food by-products were the main used materials. • Extrusion, spray-drying, and freeze-drying were the most used encapsulation methods. • Encapsulating material's concentration, probiotic strain, and process parameters should be considered. [ABSTRACT FROM AUTHOR]

This study evaluated the effects of kefir fermentation and inulin addition on the characteristics of cloudy or clarified cagaita (Eugenia dysenterica (Mart.) DC.) beverages. The products were evaluated for their physicochemical and functional characteristics, microbiological viability, and microbiota profile during refrigerated storage (7 °C, 28 days). The kefir fermentation resulted in a decrease in pH and total soluble solids and an increase in titratable acidity and alcohol content. Furthermore, it reduced sedimentation value and increased bioactive compounds (ascorbic acid and carotenoids) in cloudy beverages. The cloudy fermented beverage showed a predominance of the genus Pseudarthrobacter , while SporoLactobacillu s and Lactobacillus were the dominant genera in the clarified beverage. The inulin addition did not change the characteristics of the non-fermented beverages. Still, it increased the Lactobacillus (1.10 and 0.54 Log UFC/mL for cloudy and clarified beverages, respectively), yeast (0.62 and 0.42 Log UFC/mL for cloudy and clarified beverages, respectively), and Lactococcus (5.66 and 5.51 Log UFC/mL for cloudy and clarified beverages, respectively) viabilities during refrigerated storage and resulted in cloudy fermented products with less sedimentation and greater functional properties (antioxidant and anti-diabetic activities). The cloudy beverage added with inulin showed a greater abundance of the Ziziphu s genera (94%), while the clarified beverage added with inulin showed a predominance of Pseudarthrobacter (85.51%). During storage, there was a decrease in total soluble solids and an increase in pH and the concentration of bioactive compounds (phenolic compounds and ascorbic acid) in kefir-fermented beverages. It is concluded that kefir fermentation and inulin addition contribute to the physicochemical, functional, and microbiological characteristics of cagaita beverages. [Display omitted] [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and safety of the combination of olaparib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC) and germinal BRCA mutations (gBRCAm). OPHELIA (NCT03931551) was a single-arm, open-label, phase 2 clinical trial. Patients aged ≥18 years diagnosed with HER2-positive ABC with germinal deleterious mutations in BRCA1 or BRCA2 who had received at least one prior systemic regimen for advanced disease were enrolled. Patients received olaparib plus trastuzumab until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was investigator-assessed clinical benefit rate for at least 24 weeks as per RECIST v.1.1. Key secondary endpoints included overall response rate (ORR) and safety profile. A total of 68 pre-treated HER2-positive ABC patients were screened. Due to slow accrual the trial was stopped after enrolling 5 patients instead of the planned sample size of 20. Four patients achieved clinical benefit (80.0 %, 95 % CI; 28.4–99.5, p < 0.001) and the primary endpoint was met. The ORR was 60.0 % (95 % CI; 14.7–94.7), including one complete response. Four (80.0 %) patients experienced at least one treatment-related treatment-emergent adverse event (TEAE). Most TEAEs were grade 1 or 2. There were no treatment-related deaths and no new safety signals were identified. This study suggests that the combination of olaparib plus trastuzumab may be effective and safe in pre-treated patients with HER2-positive g BRCA m ABC. This ABC patient population should be further studied and not be pre-emptively excluded from clinical trials of targeted therapy for BRCA1/2 -driven cancers. • HER2 overexpression in g BRCA m is infrequent. • Olaparib plus trastuzumab showed promising efficacy in patients with HER2-positive ABC and g BRCA m. • This patient population should not be excluded from clinical trials of targeted therapy for BRCA1/2 -driven cancers. [ABSTRACT FROM AUTHOR]

Providing adequate care for the person with a fragility fracture is essential to prevent recurrences. A key strategy involves training by improving nursing care in the fields of osteoporosis and fragility fractures. However, in Portugal, there is no report on the level of knowledge of nurses, nor experimental studies on how to improve it. The study aimed to assess the knowledge of Rehabilitation Nurses in Portugal on osteoporosis and fragility fractures. Additionally, it sought to evaluate the impact of a specific educational programme on nurses' knowledge. In Phase I, a cross-sectional study involved 452 participants, utilizing a 26-question knowledge test. In Phase II, a quasi-experimental study included 42 nurses from 28 hospitals, subjected to a 30-h hybrid educational programme. The program comprised 9 online (2 h 30 min each) and 2 live sessions, covering assessment, pharmacological and non-pharmacological treatment, monitoring, project planning, consultations, and outcome indicators measurement. A before-and-after programme knowledge test was administered. Phase I revealed an average knowledge score of 69.6%. In Phase II, there was a significant improvement with programme (70.4% vs. 85.8%, p < 0.01). Specialized nurses performed better than non-specialized nurses (80% vs. 75%, p = 0.011), and those from orthopaedic services showed the greatest improvement (92% vs. 83%, p = 0.014). Rehabilitation Nurses in Portugal have room to improve their knowledge of osteoporosis and fragility fractures. The hybrid educational programme proved effective in improving nurses' knowledge, especially among specialist and orthopaedic service nurses. We hope that this knowledge can be translated into continuous improvement in healthcare provision. [ABSTRACT FROM AUTHOR]

In addition to the long-established role in erythropoiesis, erythropoietin (Epo) has protective functions in a variety of tissues, including the heart. This is the most affected organ in chronic Chagas disease, caused by the protozoan Trypanosoma cruzi. Despite seven million people being infected with T. cruzi worldwide, there is no effective treatment preventing the disease progression to the chronic phase when the pathological involvement of the heart is often observed. Chronic chagasic cardiomyopathy has a wide variety of manifestations, like left ventricular systolic dysfunction, dilated cardiomyopathy, and heart failure. Since Epo may help maintain cardiac function by reducing myocardial necrosis, inflammation, and fibrosis, this study aimed to evaluate whether the Epo has positive effects on experimental Chagas disease. For that, we assessed the earlier (acute phase) and also the later (chronic phase) use of Epo in infected C57BL/6 mice. Blood cell count, biochemical parameters, parasitic load, and echocardiography data were evaluated. In addition, histopathological analysis was carried out. Our data showed that Epo had no trypanocide effect nor did it modify the production of anti- T. cruzi antibodies. Epo-treated groups exhibited parasitic burden much lower in the heart compared to blood. No pattern of hematological changes was observed combining infection with treatment with Epo. Chronic Epo administration reduced CK-MB serum activity from d0 to d180, irrespectively of T. cruzi infection. Likewise, echocardiography and histological results indicate that Epo treatment is more effective in the chronic phase of experimental Chagas disease. Since treatment is one of the greatest challenges of Chagas disease, alternative therapies should be investigated, including Epo combined with benznidazole. [Display omitted] • Mice treated with erythropoietin had lower levels of CK-MB regardless of T. cruzi infection. • Neither heart fibrosis nor necrosis was seen with erythropoietin in the chronic phase of infection. • Heart perivascular inflammation was less frequent with erythropoietin in the chronic phase. • The ejection fraction was normal with erythropoietin in the chronic phase of infection. • Treatment with erythropoietin in the chronic phase appears to have better results. [ABSTRACT FROM AUTHOR]

[Display omitted] • 250 to 30 Ma alkaline and tholeiitic magmatism related to metasomatic processes. • The Sr-Nd-Hf-Pb-Os isotope data are compatible with recycled mantle sources. • West Gondwana break-up and dispersal in South America played a crucial role in mantle-derived magmatism. • Heterogeneous mantle domains in the South American SCLM. For over 50 years, Mesozoic tholeiites, kimberlites and carbonatites from the South American platform have been enabled the understanding of melting processes in the Earth's upper mantle. However, the genetic relationship between alkaline and tholeiitic magmatism remains unknown. In this context, an extensive review, based on a compilation of published geochemical and isotopic data, shows an integrated evolution for mantle-derived magmatism in South America. The K-rich alkaline-carbonatite intrusions occur widespread through time at 255–209 Ma, 146–106 Ma and 91–71 Ma. Moreover, the Na-rich magmatic episodes are also documented at 130–120 Ma and 66–32 Ma. Tholeiitic basaltic lavas and dikes are recorded at ∼200 Ma in Northern Brazil and mainly between 134 and 131 Ma in the Paraná Magmatic Province. Simultaneous tholeiitic lavas and carbonatitic complexes are related to near isothermal decompression of enriched asthenospheric and lithospheric mantle sources at different depths (80–200 km). Likewise, the 267–226 Ma kimberlites in the Amazonian Craton, ∼128 Ma Rosário kimberlite in the Rio de la Plata Craton and 88–80 Ma Alto Paranaíba kimberlites in the western edge of the São Francisco Craton provide evidence for deeper (>200 km) metasomatized mantle sources. Compiled numerical, geophysical and geological data support the proposal that the thickness of the lithosphere, extension rates and the presence of previous weak crustal structures contributed to the generation and emplacement of multiple tholeiitic and alkaline intrusions from 250 to 30 Ma. We propose that several crustal extension events induced repeated thermal convection cells in the metasomatized asthenosphere, which triggered partial melting in the previously enriched and heterogeneous lithospheric mantle. The local mantle composition, depth and crustal extension ratios controlled the magma composition. Thus, West Gondwana break-up and dispersal played a crucial role in the Mesozoic to Paleogene melting processes of the metasomatized mantle in South America. [ABSTRACT FROM AUTHOR]

Cardiac implantable electronic devices, including implantable cardioverter-defibrillators and therapy, are part of guideline-indicated treatment for a subset of patients with heart failure with reduced ejection fraction. Current technological advancements in cardiac implantable electronic devices have allowed the detection of specific physiological parameters that are used to forecast clinical decompensation through algorithmic, multiparameter remote monitoring. Other recent emerging technologies, including cardiac contractility modulation and baroreflex activation therapy, may provide symptomatic or physiological benefits in patients without indications for cardiac resynchronization. Our goal in this state-of-the-art review is to describe the new commercially available technologies, their purported mechanisms of action, and the evidence surrounding their clinical roles, limitations and future directions. Finally, we underline the need for standardized workflow and close interdisciplinary management of this population to ensure the delivery of high-quality care. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the presence of alien phytoplankton species transported through ballast water of ships that docked on the Amazon coast. Phytoplankton samples were collected from 25 ships between 2012 and 2014, revealing 215 identified species, mostly comprising oceanic planktonic marine species. However, several coastal and freshwater species not yet documented on the Maranhão coast were also observed. The identification of several coastal and freshwater species not yet recorded for Amazonian environments in the ballast water of the Ponta da Madeira Maritime Terminal (TMPM), as well as toxic microalgae genera such as the dinoflagellates Alexandrium and Gymnodinium and of some diatom species from the genus Pseudo-nitzchia , raises concerns regarding the possibility of introducing species. This indicates that ballast water can be responsible for the introduction of alien species in Amazonian aquatic environments, thereby highlighting the TMPM as a critical hotspot in the Amazonian region. [Display omitted] • Ballast water phytoplankton from Northern Brazilian port areas. • Cargo ships as the main pathway of species introduction. • Alien phytoplankton species hotspot for the Amazon littoral. • New records of non-indigenous phytoplankton species for the Amazon coast. [ABSTRACT FROM AUTHOR]

• Mutations of coronaviruses, eg SARS-CoV-2, challenge developing effective antivirals. • Under controlled conditions, narrow-band UVA reduces SARS-CoV-2 viral load in vitro. • Narrow-band UVA intra- and extracellular antiviral effects are variant-independent. • UVA exposure activates canonical pathways, including interferon signaling. Under controlled settings, narrow-band ultraviolet A (UVA) exposure exerts antiviral effects both in vivo and in vitro. The effect is thought to be mediated via direct effect on viral particles and indirectly, by modulation of metabolic pathways of host cells. We aimed to explore the extracellular and intracellular antiviral effects of UVA exposure against Alpha, Beta, and Delta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vero E6 kidney normal epithelial cells and human tracheal epithelial cells were infected with Alpha, Beta, and Delta variants in a BSL-3 laboratory. To assess extracellular effects, SARS-CoV-2 variants were directly exposed to a single dose of UVA prior to infection of the host cells (Vero E6 kidney normal epithelial cells and human tracheal epithelial cells) The intracellular effects of UVA were assessed by first infecting the cells with SARS-CoV-2 variants followed by UVA treatment of infected cell monolayers. Efficacy was quantified by both plaque reduction assay and quantitative real-time polymerase chain reaction. Additionally, transcriptomic analysis was performed on exposed Vero E6 cells to assess differentially expressed genes and canonical pathways as compared to controls. SARS-CoV-2 Alpha, Beta and Delta variants are susceptible to UVA exposure prior to infection of Vero E6 cells. Importantly, the UVA-driven reduction in Delta variant load could be reproduced in human primary tracheal cells. Beta and Delta variants load also significantly decreased during Vero E6 cells intracellular experiments. UVA-driven reductions in viral loads ameliorate several host metabolic pathways, including canonical pathways related to viral infection and interferon signaling. Narrow-band UVA exhibits both extracellular effects on SARS-CoV-2 viral particles and intracellular effects on infected cells with SARS-CoV-2. Efficacy appears to be variant independent. [ABSTRACT FROM AUTHOR]

Objective: The present double-blind randomized clinical trial aimed to compare the efficacy of conservative treatment and articular lavage, either alone or combined, to reduce joint pain and improve mandibular opening.Study Design: The sample consisted of patients presenting with limited mouth opening and joint pain. The diagnosis was made according to the diagnostic criteria for temporomandibular disorders guideline and confirmed by magnetic resonance imaging. Sixty patients were selected and randomly allocated to 4 groups of 15 patients each with different treatments: group A (conservative), group B (conservative + medication), group C (arthrocentesis), and group D (arthrocentesis + medication). The groups were compared in terms of maximal interincisal opening and pain.Results: The average age of the patients was 34.17 ± 13.1 years, 88.1% were women, 72.9% had internal derangement, 54% had joint sounds, and 55.9% presented with locking. Clinical improvement was noted in all parameters compared with baseline in all groups (P < .005), but no significant differences were observed when the groups were compared (P > .05).Conclusions: Both arthrocentesis and conservative modalities were efficient treatments to reduce joint pain and increase mandibular opening. [ABSTRACT FROM AUTHOR]