A Pediatric Gastric Dieulafoy Lesion: A Case Report and Literature Review.

This report presents a case of a 16-year-old male with severe upper gastrointestinal bleeding caused by a Dieulafoy lesion (DL). A DL is a rare but life-threatening condition characterized by sudden and massive bleeding from a small arterial vessel in the gastrointestinal (GI) tract. Diagnosis is often made through esophagogastroduodenoscopy (EGD), which reveals an enlarged submucosal blood vessel. The patient was successfully treated with adrenaline injection and hemoclipping during EGD. This case highlights the importance of considering a DL as a potential cause of severe upper GI bleeding in pediatric patients and emphasizes the significance of early recognition and intervention to achieve favorable outcomes. Additional investigation is required to enhance our comprehension of the occurrence, etiology, and most effective approaches to managing DLs in pediatric patients.

New Approaches to the Prevention of Visceral Leishmaniasis: A Review of Recent Patents of Potential Candidates for a Chimeric Protein Vaccine.

The development of prophylactic vaccines is important in preventing and controlling diseases such as visceral leishmaniasis (VL), in addition to being an economic measure for public health. Despite the efforts to develop a vaccine against human VL caused by Leishmania infantum, none is available, and the focus has shifted to developing vaccines against canine visceral leishmaniasis (CVL). Currently, commercially available vaccines are targeted at CVL but are not effective. Different strategies have been applied in developing and improving vaccines, such as using chimeric proteins to expand vaccine coverage. The search for patents can be a way of tracking vaccines that have the potential to be marketed. In this context, the present work presents a summary of immunological aspects relevant to VL vaccine development with a focus on the composition of chimeric protein vaccines for CVL deposited in patent banks as an important approach for biotechnological development. The resulting data could facilitate the screening and selection of antigens to compose vaccine candidates with high performance against VL.

Use of Various Sugarcane Byproducts to Produce Lipid Extracts with Bioactive Properties: Physicochemical and Biological Characterization.

Sugarcane, a globally cultivated crop constituting nearly 80% of total sugar production, yields residues from harvesting and sugar production known for their renewable bioactive compounds with health-promoting properties. Despite previous studies, the intricate interplay of extracts from diverse sugarcane byproducts and their biological attributes remains underexplored. This study focused on extracting the lipid fraction from a blend of selected sugarcane byproducts (straw, bagasse, and filter cake) using ethanol. The resulting extract underwent comprehensive characterization, including physicochemical analysis (FT-IR, DSC, particle size distribution, and color) and chemical composition assessment (GC-MS). The biological properties were evaluated through antihypertensive (ACE), anticholesterolemic (HMG-CoA reductase), and antidiabetic (alpha-glucosidase and Dipeptidyl Peptidase-IV) assays, alongside in vitro biocompatibility assessments in Caco-2 and Hep G2 cells. The phytochemicals identified, such as ß-sitosterol and 1-octacosanol, likely contribute to the extract's antidiabetic, anticholesterolemic, and antihypertensive potential, given their association with various beneficial bioactivities. The extract exhibited substantial antidiabetic effects, inhibiting α-glucosidase (5-60%) and DPP-IV activity (25-100%), anticholesterolemic potential with HMG-CoA reductase inhibition (11.4-63.2%), and antihypertensive properties through ACE inhibition (24.0-27.3%). These findings lay the groundwork for incorporating these ingredients into the development of food supplements or nutraceuticals, offering potential for preventing and managing metabolic syndrome-associated conditions.

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.

A geometry-based finite element tool for evaluating mitral valve biomechanics.

Mitral valve function depends on its complex geometry and tissue health, with alterations in shape and tissue response affecting the long-term restorarion of function. Previous computational frameworks for biomechanical assessment are mostly based on patient-specific geometries; however, these are not flexible enough to yield a variety of models and assess mitral closure for individually tuned morphological parameters or material property representations. This study details the finite element approach implemented in our previously developed toolbox to assess mitral valve biomechanics and showcases its flexibility through the generation and biomechanical evaluation of different models. A healthy valve geometry was generated and its computational predictions for biomechanics validated against data in the literature. Moreover, two mitral valve models including geometric alterations associated with disease were generated and analysed. The healthy mitral valve model yielded biomechanical predictions in terms of valve closure dynamics, leaflet stresses and papillary muscle and chordae forces comparable to previous computational and experimental studies. Mitral valve function was compromised in geometries representing disease, expressed by the presence of regurgitating areas, elevated stress on the leaflets and unbalanced subvalvular apparatus forces. This showcases the flexibility of the toolbox concerning the generation of a range of mitral valve models with varying geometric definitions and material properties and the evaluation of their biomechanics.

Oromandibular Dystonia as a Side Effect of Methotrexate.

Oromandibular dystonia is a focal dystonia characterized by involuntary movements of the jaw, oropharynx, lips, and tongue. The diagnosis of oromandibular dystonia is clinical and can be complex. For effective treatment, it is essential to understand its underlying etiology. A 70-year-old man was referred to our center with a diagnosis of Meige's syndrome, which had been present for five and a half years, for receiving botulinum toxin-A (BoNT-A) injections. Upon physical examination, he exhibited oromandibular dystonia, with a score of 177 points on the Oromandibular Dystonia Rating Scale (OMDRS). He had a history of taking methotrexate for six years, as he was diagnosed with psoriatic arthritis during that time. The possibility of methotrexate-induced dystonia was considered. A switch from methotrexate to sulfasalazine was initiated. Subsequently, the patient showed progressive improvement in his symptoms, as reflected by an OMDRS score of 103 points. After eight weeks, the medical team decided to supplement the treatment with BoNT-A injections, resulting in an OMDRS score of 75. While there is currently no definitive evidence linking the use of methotrexate to the development of dystonia, it is advisable to consider oromandibular dystonia as a potential side effect of methotrexate until more robust evidence becomes available.

Transmission-Blocking Vaccines for Canine Visceral Leishmaniasis: New Progress and Yet New Challenges.

Dogs with visceral leishmaniasis play a key role in the transmission cycle of Leishmania infantum to humans in the urban environment. There is a consensus regarding the importance of developing a vaccine to control this disease. Despite many efforts to develop a protective vaccine against CVL, the ones currently available, Leish-tec® and LetiFend®, have limited effectiveness. This is due, in part, to the complexity of the immune response of the naturally infected dogs against the parasite and the complexity of the parasite transmission cycle. Thus, strategies, such as the development of a transmission-blocking vaccines (TBVs) already being applied to other vector-borne diseases like malaria and dengue, would be an attractive alternative to control leishmaniasis. TBVs induce the production of antibodies in the vertebrate host, which can inhibit parasite development in the vector and/or interfere with aspects of vector biology, leading to an interruption of parasite transmission. To date, there are few TBV studies for CVL and other leishmaniasis forms. However, the few studies that exist show promising results, thus justifying the further development of this approach.

Prognostic impact of red blood cell distribution width in chronic heart failure patients with left ventricular dysfunction.

AIMS: Red blood cell (RBC) distribution width (RDW) measures RBC variations in size. Higher RDW values have been associated with poor outcome in acute heart failure (HF). We aimed to assess the prognostic impact of the RDW in chronic HF. METHODS: We retrospectively analysed a cohort of chronic HF patients with left ventricular systolic dysfunction followed in our HF clinic between January 2012 and May 2018. Patients with missing data concerning RDW were excluded. Patients were categorized according to RDW tertiles: ≤13.5%; between 13.5 and 14.7%; and >14.7%. Patients were followed until January 2021; all-cause mortality was the end point analysed. The association of RDW with all-cause mortality was assessed with a Cox-regression analysis. Two multivariate models were built. RESULTS: We studied 860 chronic HF patients, 66.4% males, mean age 70 (standard deviation, SD 13) years. Patients were followed for a median of 49 (29-82) months. During this period, 423 (49.2%) patients died. Mortality increased with increasing RDW tertiles. Patients with RDW >14.7% had a HR of mortality of 1.95 (1.47-2.58), p < 0.001 (model 1) and of 1.81 (1.35-2.41), p < 0.001 (model 2) when compared with those with RDW ≤13.5. Patients in the second RDW tertile had an all-cause death HR of 1.47 (1.12-1.93) and of 1.44 (1.09-1.90) in models 1 and 2, respectively. CONCLUSIONS: Chronic HF patients with RDW values >14.7% presented an almost 2-fold higher risk of dying in the long term than those with RDW <13.5%. RDW is a widely available and easily measured parameter that can help clinicians in the risk stratification of chronic HF patients.

Influence of weight variation on long-term mortality of patients with heart failure.

BACKGROUND: In heart failure, weight loss predicts dismal prognosis. Weight variations have not been addressed in obese patients with heart failure. AIM: To study the impact of weight variation on heart failure mortality according to body mass index strata. METHODS: Retrospective study of patients with chronic heart failure with left ventricular ejection fraction<50%. Only patients with ≥1 year of follow-up were included. Patients with missing data for body mass index at the index and 1-year appointments were excluded. Patients were classified into three groups according to weight variation: weight gain>5%; weight loss>5%; and weight stability. Follow-up was set from the 1-year appointment. Cox-regression analysis was used to assess the prognostic impact of weight variation. RESULTS: We studied 589 patients: 69.8% male; mean age, 69 years. Over 1 year, 148 patients (25.1%) gained>5% weight, 97 (16.5%) lost>5% weight and the remaining 344 were weight-stable. During 49 months of median follow-up, 248 patients died. Patients who lost>5% of their weight presented a higher death risk than the others (hazard ratio 1.61, 95% confidence interval 1.18-2.19). After multivariable adjustment, the hazard ratio for death for low/normal-weight patients who lost>5% of their weight was 1.81 (95% confidence interval 1.02-3.21; P=0.04) compared with the others. Among the overweight, those who lost>5% of their weight had a hazard ratio of 2.34 (95% confidence interval 1.32-4.12). In the initially obese subgroup, weight loss>5% was not associated with prognosis (hazard ratio 1.08, 95% confidence interval 0.53-2.19). CONCLUSIONS: Weight loss predicted mortality in low/normal-weight and overweight patients with heart failure. However, in obese patients, significant weight loss did not predict poorer survival. Weight loss should not be discouraged in obese patients with heart failure.

Accuracy of serological tests in diagnosing mucosal leishmaniasis.

In this serum panel-based study, we evaluated the accuracy of serological tests originally developed for visceral leishmaniasis (VL), for diagnosis of mucosal leishmaniasis (ML). A total of five tests were evaluated, four of which are registered at the National Agency of Sanitary Surveillance (Agência Nacional de Vigilância Sanitária-ANVISA) (RIDASCREEN® Leishmania Ab from R-Biopharm AG., Leishmania ELISA IgG + IgM from Vircell S.L., IFI Leishmaniose Humana-BioManguinhos, and IT-LEISH® from Bio-Rad Laboratories, Inc.), and the other a direct agglutination test (DAT-LPC) prototype kit developed at Fiocruz. The panel was composed of 40 serum samples from patients with confirmed ML and 20 from patients with mucosal involvement and negative parasitological/molecular tests for leishmaniasis and confirmation of another etiology. All cases were treated from 2009 to 2016 in a referral center for leishmaniasis in Belo Horizonte, Minas Gerais, Brazil (Instituto René Rachou, Fiocruz). Diagnostic accuracy, based on the cut-off point for VL diagnosis, was 86.2% with RIDASCREEN® Leishmania Ab, 73.3% with Leishmania ELISA IgG + IgM, and 66.7% with IFI Leishmaniose Humana, while IT-LEISH® and DAT-LPC had the lowest accuracy (38.3%), despite high specificity (100% and 95%, respectively). New cut-off points defined with sera from ML patients improved accuracy from 86.2 to 89% (p = 0.64) and 73.3 to 88% (p = 0.04) for RIDASCREEN® Leishmania Ab and Leishmania ELISA IgG + IgM, respectively. Moreover, these tests presented greater sensitivity and immunoreactivity in patients with moderate/severe clinical ML forms. The data of this study suggest that ELISA assays can contribute to laboratory diagnosis, especially for patients with moderate or severe mucosal involvement.

Strategies to Assess the Impact of Sustainable Functional Food Ingredients on Gut Microbiota.

Nowadays, it is evident that food ingredients have different roles and distinct health benefits to the consumer. Over the past years, the interest in functional foods, especially those targeting gut health, has grown significantly. The use of industrial byproducts as a source of new functional and sustainable ingredients as a response to such demands has raised interest. However, the properties of these ingredients can be affected once incorporated into different food matrices. Therefore, when searching for the least costly and most suitable, beneficial, and sustainable formulations, it is necessary to understand how such ingredients perform when supplemented in different food matrices and how they impact the host's health. As proposed in this manuscript, the ingredients' properties can be first evaluated using in vitro gastrointestinal tract (GIT) simulation models prior to validation through human clinical trials. In vitro models are powerful tools that mimic the physicochemical and physiological conditions of the GIT, enabling prediction of the potentials of functional ingredients per se and when incorporated into a food matrix. Understanding how newly developed ingredients from undervalued agro-industrial sources behave as supplements supports the development of new and more sustainable functional foods while scientifically backing up health-benefits claims.

Lifestyle Medicine in Diabetes Care: The Lifedoc Health Model.

Introduction: The relevance of lifestyle medicine in diabetes treatment is now incorporated in clinical practice guidelines but finding an exemplar for the creation of a Lifestyle Medicine Program (LMP) is a difficult task. Aim: To use Lifedoc Health (LDH) as a LMP exemplar by describing their multidisciplinary team (MDT) approach to diabetes care along with tactics to address sustainability challenges. Results: The LDH model facilitates early activation of patients with diabetes and other cardiometabolic risk factors, MDT approaches, and protocols/policies that are able to overcome barriers to equitable healthcare in the community. Specific programmatic targets are clinical outcomes, effective dissemination, economic viability, and sustainability. Infrastructure centers on patient-driven problem-based visits, shared medical appointments, telemedicine, and patient tracking. Further discussions on program conceptualization and operationalization are provided. Conclusion: Even though strategic plans for LMPs that specialize in diabetes care are well represented in the literature, implementation protocols, and performance metrics are lacking. The LDH experience provides a starting point for those healthcare professionals interested in translating ideas into action.

Clinical Manifestations of Human Exposure to Fungi.

Biological particles, along with inorganic gaseous and particulate pollutants, constitute an ever-present component of the atmosphere and surfaces. Among these particles are fungal species colonizing almost all ecosystems, including the human body. Although inoffensive to most people, fungi can be responsible for several health problems, such as allergic fungal diseases and fungal infections. Worldwide fungal disease incidence is increasing, with new emerging fungal diseases appearing yearly. Reasons for this increase are the expansion of life expectancy, the number of immunocompromised patients (immunosuppressive treatments for transplantation, autoimmune diseases, and immunodeficiency diseases), the number of uncontrolled underlying conditions (e.g., diabetes mellitus), and the misusage of medication (e.g., corticosteroids and broad-spectrum antibiotics). Managing fungal diseases is challenging; only four classes of antifungal drugs are available, resistance to these drugs is increasing, and no vaccines have been approved. The present work reviews the implications of fungal particles in human health from allergic diseases (i.e., allergic bronchopulmonary aspergillosis, severe asthma with fungal sensitization, thunderstorm asthma, allergic fungal rhinosinusitis, and occupational lung diseases) to infections (i.e., superficial, subcutaneous, and systemic infections). Topics such as the etiological agent, risk factors, clinical manifestations, diagnosis, and treatment will be revised to improve the knowledge of this growing health concern.

A Review of Major Patents on Potential Malaria Vaccine Targets.

Malaria is a parasitic infection that is a great public health concern and is responsible for high mortality rates worldwide. Different strategies have been employed to improve disease control, demonstrating the ineffectiveness of controlling vectors, and parasite resistance to antimalarial drugs requires the development of an effective preventive vaccine. There are countless challenges to the development of such a vaccine directly related to the parasite's complex life cycle. After more than four decades of basic research and clinical trials, the World Health Organization (WHO) has recommended the pre-erythrocytic Plasmodium falciparum (RTS, S) malaria vaccine for widespread use among children living in malaria-endemic areas. However, there is a consensus that major improvements are needed to develop a vaccine with a greater epidemiological impact in endemic areas. This review discusses novel strategies for malaria vaccine design taking the target stages within the parasite cycle into account. The design of the multi-component vaccine shows considerable potential, especially as it involves transmission-blocking vaccines (TBVs) that eliminate the parasite's replication towards sporozoite stage parasites during a blood meal of female anopheline mosquitoes. Significant improvements have been made but additional efforts to achieve an efficient vaccine are required to improve control measures. Different strategies have been employed, thus demonstrating the ineffectiveness in controlling vectors, and parasite resistance to antimalarial drugs requires the development of a preventive vaccine. Despite having a vaccine in an advanced stage of development, such as the RTS, S malaria vaccine, the search for an effective vaccine against malaria is far from over. This review discusses novel strategies for malaria vaccine design taking into account the target stages within the parasite's life cycle.

Sugarcane Straw Polyphenols as Potential Food and Nutraceutical Ingredient.

The sugarcane processing industry generates a large amount of straw, which has a negative environmental impact, and high costs are associated with their elimination, wasting their potential bioactive value attributed to their richness in polyphenols. In this study, an ethanolic extract produced from sugarcane straw was screened for its phenolic compounds content, and the potential use of this extract in the development of a food ingredient was further evaluated. Fifty different secondary metabolites belonging to the hydroxybenzoic acids, hydroxycinnamic acids, and flavonoids were identified by liquid chromatography-electrospray ionization-ultrahigh-resolution-quadrupole time of flight-mass spectrometry (LC-ESI-UHR-QqTOF-MS). The predominant phenolic compounds found were 4-hydroxybenzaldehyde, chlorogenic acid, and 5-O-feruloylquinic acid. The obtained extracts showed strong potential as food preservatives by exhibiting (a) antioxidant activity using both 2.2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt radical cation (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods; and (b) antimicrobial capacity, with a minimum inhibitory concentration of 50 mg/mL for Staphylococcus aureus, 74% inhibition for Bacillus cereus, and 44% for Salmonella enterica; and (c) the capacity to inhibit a food browning enzyme, tyrosinase (28-73% for 1-8 mg/ mL). Moreover, the extracts showed antidiabetic potential by inhibiting the enzymes α-glucosidase (15-38% for 1.25-5.00 mg/mL) and dipeptidyl peptidase-IV (DPP-IV) (62-114% for 0.31-5.00 mg/mL). The extract (0.625 mg/mL) also exhibited the capacity to reduce proinflammatory mediators (i.e., interleukins 6 and 8, and tumor necrosis factor alpha) when Caco-2 cells were stimulated with interleukin 1 beta. Thus, sugarcane straw extract, which is rich in phenolic compounds, showed high potential to be used in the development of food-preservative ingredients owing to its antioxidant and antimicrobial potential, and to be explored as a food supplement in diabetes prevention and as coadjuvant to reduce intestinal inflammation by reducing proinflammatory mediators.

Effects of the Interculturality and Mindfulness Program (PIM) on University Students: A Quasi-Experimental Study.

Rates of mental health issues have been increasing among university students. This study investigates the effects of the Interculturality and Mindfulness Program (PIM) on academic students on mindfulness, emotional regulation, depression, anxiety, stress, life satisfaction, optimism, positive solitude, and loneliness. A quasi-experimental research was conducted, with pre- and post-test comparative measurements in three groups: in-person (IG), synchronous online (OG), and passive control (CG). A diverse group of students (n = 150; mean age = 25.4 ± 8.31) participated from two universities in Portugal. When compared to the CG, both active groups (IG and OG) demonstrated a beneficial interaction effect in acceptance, positive solitude, optimism, and mindfulness. The IG demonstrated a positive interaction effect in awareness and satisfaction with life, whereas the OG indicated a favorable interaction effect in impulse. When analyzing the intra-group effects, both active groups presented a significant improvement in stress, emotion regulation, mindfulness, positive solitude, and optimism. The OG demonstrated an improvement in awareness and loneliness. The main limitations of this research are that students were not randomly assigned, and groups were heterogeneous in nationality, education level, and sex. Nonetheless, PIM has indicated beneficial results in both IG and OG, and is a promising intervention for the prevention of mental health issues (e.g., stress, difficulties in emotional regulation, and loneliness), as well as for the promotion of well-being (e.g., positive solitude, mindfulness, life satisfaction, and optimism).

Thermofluor-Based Optimization Strategy for the Stabilization of Recombinant Human Soluble Catechol-O-Methyltransferase.

Catechol-O-methyltransferase (COMT) has been involved in a number of medical conditions including catechol-estrogen-induced cancers and a great range of cardiovascular and neurodegenerative diseases such as Parkinson's disease. Currently, Parkinson's disease treatment relies on a triple prophylaxis, involving dopamine replacement by levodopa, the use of aromatic L-amino acid decarboxylase inhibitors, and the use of COMT inhibitors. Typically, COMT is highly thermolabile, and its soluble isoform (SCOMT) loses biological activity within a short time span preventing further structural and functional trials. Herein, we characterized the thermal stability profile of lysate cells from Komagataella pastoris containing human recombinant SCOMT (hSCOMT) and enzyme-purified fractions (by Immobilized Metal Affinity Chromatography-IMAC) upon interaction with several buffers and additives by Thermal Shift Assay (TSA) and a biological activity assessment. Based on the obtained results, potential conditions able to increase the thermal stability of hSCOMT have been found through the analysis of melting temperature (Tm) variations. Moreover, the use of the ionic liquid 1-butyl-3-methylimidazolium chloride [C4mim]Cl (along with cysteine, trehalose, and glycerol) ensures complete protein solubilization as well as an increment in the protein Tm of approximately 10 °C. Thus, the developed formulation enhances hSCOMT stability with an increment in the percentage of activity recovery of 200% and 70% when the protein was stored at 4 °C and -80 °C, respectively, for 12 h. The formation of metanephrine over time confirmed that the enzyme showed twice the productivity in the presence of the additive. These outstanding achievements might pave the way for the development of future hSCOMT structural and biophysical studies, which are fundamental for the design of novel therapeutic molecules.

Screening of Natural Molecules as Adjuvants to Topical Antibiotics to Treat Staphylococcus aureus from Diabetic Foot Ulcer Infections.

Diabetic foot ulcers (DFUs) are a common result of a complex secondary complication of diabetes mellitus. More than half of DFUs become infected due to frequent colonization with Staphylococcus aureus. The use of topical antibiotics is proposed, especially in combination with natural adjuvants, to minimize the negative impacts caused by generalized use of systemic antibiotics. In this study, 13 different phytochemicals-namely chalcone, juglone, cinnamic acid, trigonelline, Furvina-and four nitrovinylfuran derivatives-guaiazulene, α-bisabolol, farnesol and nerolidol-were selected to be tested as antibiotic enhancers. After minimum inhibitory and bactericidal concentration (MIC and MBC) determination of each molecule against different strains of S. aureus, including clinical isolates from diabetic foot wounds (CECT 976, Xu212, SA 1199B, RN4220, MJMC102, MJMC109, MJMC110 and MJMC111), their potentiation effects on the antibiotics fusidic acid, mupirocin, gentamicin, oxacillin and methicillin were evaluated through the disc diffusion method. Farnesol at sub-MIC was able to restore the activity of methicillin and oxacillin on the MJMC102 and MJMC111 strains, as well as two MRSA clinical isolates, and potentiated the effect of the remaining antibiotics. The results obtained demonstrate the great potential for the topical application of phytochemicals and derivatives as antibiotic resistance modifier agents to combat multidrug resistance in bacterial wound infections.

Prognostic impact of neurohormonal modulation in very old patients with chronic heart failure.

BACKGROUND: A gap in evidence exists concerning the survival-benefit of neurohormonal blockade in older patients with chronic heart failure (HF). The purpose of our study was to investigate the neurohormonal modulation therapy in older HF patients. METHODS: We retrospectively analysed data on chronic HF patients with systolic dysfunction from January 2012 to May 2018 at a central tertiary academic hospital in Porto, Portugal. Very old (VO) patients were those ≥80 years. Endpoint under analysis: all-cause mortality; patients were followed until January 2021. The prognostic impact of beta-blockers (BBs) and renin-angiotensin system inhibitors (RASi) use was assessed with a Cox-regression analysis adjusting for confounders. RESULTS: We studied 934 patients, 65.5% male; 45.3% had ischemic HF. BBs were used in 92.2% and RASi in 83.5%; 255 (27.3%) were VO patients. VO more often presented co-morbidities, were more symptomatic, presented worse renal function and higher BNP levels. BB prescription was similar in VO and non-VO patients, however RASi were less used in VO: 74.9% versus 86.7%, respectively. During a median follow-up of 47 months, 479 (51.3%) patients died: 71.4% among VO versus 43.7% in non-VO. BBs increased survival both in non-VO and VO-multivariate adjusted HRs of 0.57 (95% CI: 0.38-0.85) and 0.59 (0.36-0.97), respectively. A survival-benefit was also observed with RASi-adjusted HR of 0.71 (0.50-1.01) and 0.59 (0.42-0.83) in non-VO and VO. CONCLUSIONS: VO patients with chronic HF with systolic dysfunction have a very ominous outcome. Neurohormonal modulation therapy appears to portend survival-benefit also in this particularly vulnerable subgroup of patients.

HLA DQ2/DQ8 haplotypes and anti-transglutaminase antibodies as celiac disease markers in a pediatric population with type 1 diabetes mellitus.

Objective: Evaluate the celiac disease (CD) markers, within the scope of its screening, in a pediatric population with diagnosis of type 1 diabetes (T1D) at Hospital de Braga (HB) and determine the prevalence of CD in the sample. Reflect on CD screening algorithm applied in this pediatric population. Methods: Retrospective observational study with 94 patients diagnosed with T1D at age 10 years or younger, followed up at the HB Outpatient Diabetology Consultation, including those referred from other hospitals. Record of clinical information, IgA anti-transglutaminase and anti-endomysium and HLA DQ2/DQ8 haplotypes. Results: We obtained positive serological test for CD in 4 patients. This test had 100% sensitivity and specificity. The prevalence of CD was 4.3% (n = 4). Positive HLA screening in 84.6% of patients, with both sensitivity and negative predictive value of 100% and specificity of 16.67%. Diagnosis of CD was made on average 3.40 ± 3.32 years after the diagnosis of TD1. All cases of CD registered non-gastrointestinal manifestations, none had gastrointestinal symptoms. Conclusion: This study proved that there is a higher prevalence of CD in pediatric population with TD1, when compared to general population, and clarified the importance of CD screening. Furthermore, it was observed that serological screening for CD antibodies is an excellent screening test and HLA typing, although not the most suitable first line test, can be useful in excluding the possibility of patients with T1D developing CD.