Dietary protein from different sources escapes host digestion and is differentially modified by the microbiota.

Protein is an essential macronutrient and variations in its source and quantity have been shown to impact long-term health outcomes. Differential health impacts of dietary proteins from various sources are likely driven by differences in their digestibility by the host and subsequent availability to the intestinal microbiota. However, our current understanding regarding the fate of dietary proteins from different sources in the gut, specifically how component proteins within these sources interact with the host and the gut microbiota, is limited. To determine which dietary proteins are efficiently digested by the host and which proteins escape host digestion and are used by the gut microbiota, we used high-resolution mass spectrometry to quantify the proteins that make up different dietary protein sources before and after digestion in germ-free and conventionally raised mice. Contrary to expectation, we detected proteins from all sources in fecal samples of both germ-free and conventional mice suggesting that even protein sources with a high digestive efficiency make it in part to the colon where they can serve as a substrate for the microbiota. Additionally, we found clear patterns where specific component proteins of the dietary protein sources were used as a preferred substrate by the microbiota or were not as accessible to the microbiota. We found that specific proteins with functions that could impact host health and physiology were differentially enriched in germ-free or conventionally raised mice. These findings reveal large differences in the fate of dietary protein from various sources in the gut that could explain some of their differential health impacts.

Long-term effects of ciprofloxacin treatment on the gastrointestinal and oropharyngeal microbiome are more pronounced after longer antibiotic courses.

BACKGROUND: Urinary tract infections (UTIs) are one of the main reasons for antibiotic prescriptions in primary care. Recent studies demonstrate similar clinical outcomes with shorter antibiotics courses. Here, we investigated the differential collateral effect of ciprofloxacin treatment duration on the gastrointestinal and oropharyngeal microbiome in patients presenting with uncomplicated UTI to primary care practices in Switzerland, Belgium and Poland. METHODS: Stool and oropharyngeal samples were obtained from 36 treated patients and 14 controls at the beginning of antibiotic therapy, end of therapy and one month after end of therapy. Samples underwent shotgun metagenomics. RESULTS: At the end of therapy, patients treated with both shorter (≤7 days) and longer (>7 days) ciprofloxacin courses showed similar changes in the gastrointestinal microbiome compared to non-treated controls. After one month, most changes in patients receiving shorter courses were reversed; however, longer courses led to increased abundance of the genera Roseburia, Faecalicatena and Escherichia. Changes in the oropharynx were minor and reversed to baseline levels within one month. Ciprofloxacin resistance encoding mutations in gyrA/B and parC/E reads were observed in both treatment groups, which decreased to baseline levels after one month. An increased abundance of resistance genes was observed in the gastrointestinal microbiome after longer treatment, and correlated to increased prevalence of aminoglycoside, beta-lactam, sulphonamide, and tetracycline resistance genes. CONCLUSION: Collateral effects on the gastrointestinal community, including an increased prevalence of antimicrobial resistance genes, persists at least up to one month following longer ciprofloxacin therapy. Our data, therefore, support the use of shorter treatment duration.

Pre-and post-surgical non-functional pituitary adenomas and their relationship with high levels of serum glucose.

OBJECTIVES: This clinical, analytical, retro-prospective, auto-controlled, not randomized, and not blinded study, aimed to investigate the association of changes in the serum glucose levels with the pre-and-post changes in the size tumor in mm3 in the Non-Functional pituitary adenomas. METHODS: Pre-and post-surgical MRI, as well as the measurements in the serum glucose levels and immunohistochemical techniques were performed in all the patients in the study, with a mean followed-up until 208.57 days. A comparison was made between the reductions in tumor size of hormonally active pituitary adenomas (HSPAs) vs NFPAs. RESULTS: Seventy-four patients were included in this study, of whom, 46 were NFPAs. The decrease in the NFPAs tumor size after surgery was statistically significant (P ≤ 0.0001). The Mean of the differences of both type of tumors in mm3 were -9552 ± 10287. Pre-surgery, the mean of the HSPAs were 8.923 ± 2.078; and the NFPAs were 14.161 ± 1.912. The differences in the tumor size were statistically significant (p = 0.039). Post-surgical, the mean of the HSPAs were 2.079 ± 971, with a (p = 0.14): and the NFPAs were 4.609 ± 1.205. After surgery of the NFPAs, most of the patients-maintained serum levels ≤ 100 mg/dL, with a statistical significance (P ≤ 0.0003). CONCLUSION: This study demonstrates for the first time the correlation between the presence of pre-and post- surgical changes in the NFPAs, with modifications in the levels of serum glucose, and the comparison, pre- and post-surgical between the tumor size of HSPAs and NFPAs.

Dietary protein source strongly alters gut microbiota composition and function.

The source of protein in a persons diet affects their total life expectancy. However, the mechanisms by which dietary protein sources differentially impact human health and life expectancy are poorly understood. Dietary choices have major impacts on the composition and function of the intestinal microbiota that ultimately mediate host health. This raises the possibility that health outcomes based on dietary protein sources might be driven by interactions between dietary protein and the gut microbiota. In this study, we determine the effects of seven different sources of dietary protein on the gut microbiota in mice. We apply an integrated metagenomics-metaproteomics approach to simultaneously investigate the effects of these dietary protein sources on the gut microbiotas composition and function. The protein abundances measured by metaproteomics can provide microbial species abundances, and evidence for the phenotype of microbiota members on the molecular level because measured proteins allow us to infer the metabolic and physiological processes used by a microbial community. We showed that dietary protein source significantly altered the species composition and overall function of the gut microbiota. Different dietary protein sources led to changes in the abundance of microbial amino acid degrading proteins and proteins involved in the degradation of glycosylations on dietary protein. In particular, brown rice and egg white protein increased the abundance of amino acid degrading enzymes and egg white protein increased the abundance of bacteria and proteins usually associated with the degradation of the intestinal mucus barrier. These results show that dietary protein source can change the gut microbiotas metabolism, which could have major implications in the context of gut microbiota mediated diseases.

Binder-free all-carbon composite supercapacitors.

Carbon-based electrode materials have widely been used in supercapacitors. Unfortunately, the fabrication of the supercapacitors includes a polymeric binding material that leads to an undesirable addition of weight along with an increased charge transfer resistance. Herein, binder-free and lightweight electrodes were fabricated using powder processing of carbon nanofibers (CNFs) and graphene nanoplatelets (GNPs) resulting in a hybrid all-carbon composite material. The structural, morphological, and electrochemical properties of the composite electrodes were studied at different concentrations of GNPs. The specific capacitance (Cs) of the CNFs/GNPs composite was improved by increasing the concentration of GNPs. A maximum Cs of around 120 F g-1was achieved at 90 wt% GNPs which is around 5-fold higher in value than the pristine CNFs in 1 M potassium hydroxides (KOH), which then further increased to 189 F g-1in 6 M KOH electrolyte. The energy density of around 20 Wh kg-1with the corresponding power density of 340 W kg-1was achieved in the supercapacitor containing 90 wt% GNPs. The enhanced electrochemical performance of the composite is related to the presence of a synergistic effect and the CNFs establishing conductive/percolating networks. Such binder-free all-carbon electrodes can be a potential candidate for next-generation energy applications.

Improvement of metabolic syndrome and its components in patients who underwent transsphenoidal resection for pituitary adenoma.

BACKGROUND: Pituitary adenomas (PA) are neoplasms of pituitary adenohypophyseal cell lineage, which are the third most common cause of brain tumors among adults. Due to hormone secretion, PAs are closely related to metabolic syndrome (MetS). However, the relationship between these two entities has been scarcely studied to date. PURPOSE: This paper aims to evaluate changes in the metabolic status of patients with PA before and after surgical treatment and to look for differences in metabolic outcomes among patients according to the adenoma type and the surgery success rate. METHODS: We assessed patients with PA who went through transsphenoidal surgery for its treatment, documenting metabolic parameters before and after surgery, analyzed whole sample changes, and then stratified them according to adenoma type (nonfunctioning, somatotroph, lactotroph, and corticotroph), and surgery success (total resection, near-total resection, partial resection, subtotal resection). RESULTS: A total of 214 patients were enrolled for this study. The prevalence of MetS with AACE criteria went from 51.52% before surgery to 28.99% after surgery (P < 0.001). Hyperglycemia (HG) was the most beneficial component; it went from 56% pre-surgery to 40.51% post-surgery (P = 0.03). The total resection group had the best improvement, with a significant decrease of prevalence in MetS from 83 to 16% (P < 0.001), and every component, except hypoalphalipoproteinemia (HA): obesity went from 96 to 67% (P < 0.001), arterial hypertension (AH) 59 to 24% (P < 0.001), HG 74 to 23% (P < 0.001), and hypertriglyceridemia (HTG) from 81 to 54% (P < 0.001). According to MetS prevalence, there was no difference in the improvement according to PA type. CONCLUSION: Surgical treatment in patients with PA is associated with MetS improvement.

Effects of androgen deprivation therapy on elderly men with high-risk prostate cancer: PROSARC observational study.

INTRODUCTION: Prostatic carcinoma (PC) is a frequent neoplasm in elderly patients. Although androgen deprivation is associated with survival benefits, it is also related to adverse effects such as osteoporosis, frailty, or sarcopenia, which can negatively affect the patient's quality of life. This study aims to quantify and evaluate the prevalence of osteoporosis, frailty, or sarcopenia in elderly PC patients before and after androgen deprivation. We present data from an interim analysis. MATERIALS AND METHODS: PROSARC is a national (Spain) prospective observational study (May-2022-May-2025) still in progress in 2 hospitals. It includes patients with high-risk PC, aged ≥70 years, non-candidates for local treatment and scheduled to start androgen deprivation therapy. The following variables are analyzed: comorbidity, frailty (Fried frailty phenotype criteria), osteoporosis, sarcopenia (EWGSOP2), fat mass and muscle mass, before treatment and after 6 months of follow-up. RESULTS: A 6-month follow-up was completed by 12/25 included patients (mean age, 84 years), with a high baseline prevalence of pre-frailty/frailty (67.7%), sarcopenia (66.7%) and osteoporosis (25%). Treatment did not significantly alter these variables or comorbidity. We observed changes in body mass index (p=0.666), decreased mean value of appendicular muscle mass (p=0.01) and increased percentage of fat mass (p=0.012). CONCLUSION: In patients with high-risk PC, advanced age and a considerable prevalence of osteoporosis, frailty and sarcopenia, androgen deprivation (ADT; 6 months) produces decreased muscle mass without impact on the incidence of the known adverse effects of androgen deprivation.

Sustainable cultivation of melon landraces: Effects of grafting on the accumulation of flavor-related compounds.

Melon landraces are highly appreciated by consumers who pay price premiums to compensate for lower yields, enabling on-farm conservation. However, they are highly susceptible to soilborne diseases. This study analyses the impact of Cucurbita and Cucumis rootstocks on the accumulation of flavor-related metabolites in Spanish landraces of the Ibericus melon group, as a strategy to promote their sustainable cultivation. Scion genotype was the main factor conditioning the accumulation of sugars and acids both under standard and saline organic farming conditions. The effects of grafting on organic acid accumulation were negligible, while the effects on sugar content were significant. The latter effects were dependent on specific scion-rootstock combinations, though wild Cucumis (e.g. Fian) rootstocks represent an alternative that should be further studied. The effect on the accumulation of volatiles was limited, and again depended on specific scion-rootstock combinations. The rootstock effect even differed between populations of the same landrace.

Fumadores y riesgo de muerte hospitalaria por COVID calculado con el procesamiento de lenguaje natural de SAVANA en el ámbito de Castilla-La Mancha / Smokers and risk of hospital death by COVID calculated with SAVANA's natural language processing in the Castilla-La Mancha area

Introducción Durante la pandemia de COVID se especuló que los pacientes con el virus que tenían relación con el tabaco podrían tener una menor probabilidad de agravamiento de la enfermedad o muerte. Para evaluar si existe una asociación entre el tabaquismo y el riesgo de mortalidad intrahospitalaria se utiliza la tecnología de Big Data y Procesamiento del Lenguaje Natural (PLN) de SAVANA. Método Se llevó a cabo un estudio de cohortes retrospectivo, observacional y sin intervención basado en datos de vida real extraídos de registros médicos de toda Castilla-La Mancha utilizando las técnicas de PLN e inteligencia artificial desarrolladas por SAVANA. El estudio abarcó toda la población de esta Comunidad con historia clínica electrónica en SESCAM que presentara diagnóstico de COVID desde el 1 de marzo de 2020 al 28 de febrero de 2021. Resultados Los fumadores tienen mayor porcentaje de factores de riesgo cardiovascular (hipertensión arterial, dislipemia y diabetes), EPOC, asma, EPID, CI, ECV, TEP, cáncer en general y cáncer de pulmón en particular, bronquiectasias, insuficiencia cardíaca y antecedentes de neumonía, de forma significativa (p<0,0001). Los pacientes exfumadores, fumadores y no fumadores tienen una diferencia de edad significativa. En cuanto a las muertes hospitalarias, fueron más frecuentes en el caso de los exfumadores, siguiendo los fumadores y luego los no fumadores (p<0,0001). Conclusión Existe un mayor riesgo de mortalidad intrahospitalaria en los pacientes infectados por SARS-CoV-2 que sean fumadores activos o hayan fumado en el pasado. (AU)

Introduction During the COVID pandemic, it was speculated that patients with the virus who were smoking-related might have a lower likelihood of disease exacerbation or death. To assess whether there is an association between smoking and risk of in-hospital mortality, SAVANA's big data and natural language processing (NLP) technology is used. Method A retrospective, observational, non-interventional cohort study was conducted based on real-life data extracted from medical records throughout Castilla-La Mancha using natural language processing and artificial intelligence techniques developed by SAVANA. The study covered the entire population of this region with Electronic Medical Records in SESCAM presenting with a diagnosis of COVID from March 1, 2020 to February 28, 2021. Results Smokers had a significantly higher percentage of cardiovascular risk factors (hypertension, dyslipidemia and diabetes), COPD, asthma, IDP, IC, CVD, PTE, cancer in general and lung cancer in particular, bronchiectasis, heart failure and a history of pneumonia (P<.0001). Former smokers, current smokers and non-smokers have a significant age difference. As for in-hospital deaths, they were more frequent in the case of ex-smokers, followed by smokers and then non-smokers (P<.0001). Conclusion There is an increased risk of dying in hospital in SARS-CoV-2-infected patients who are active smokers or have smoked in the past. (AU)

Low vitamin D levels are linked with increased cardiovascular disease risk in young adults: a sub-study and secondary analyses from the ACTIBATE randomized controlled trial.

PURPOSE: Vitamin D deficiency is related to metabolic disturbances. Indeed, a poor vitamin D status has been usually detected in patients with cardiovascular disease (CVD). However, the relationship between vitamin D and CVD risk factors in young adults remains controversial at present. This study aimed to examine the association between circulating 25-hydroxivitamin D (25(OH)D) and CVD risk factors in young adults. METHODS: The present cross-sectional study included a cohort of 177 young adults aged 18-25 years old (65% women). 25(OH)D serum concentrations were assessed using a competitive chemiluminescence immunoassay. Fasting CVD risk factors (i.e., body composition, blood pressure, glucose metabolism, lipid profile, liver, and inflammatory markers) were determined by routine methods. A panel of 63 oxylipins and endocannabinoids (eCBs) was also analyzed by targeted metabolomics. RESULTS: Circulating 25(OH)D concentrations were inversely associated with a wide range of CVD risk factors including anthropometrical (all P ≤ 0.005), body composition (all P ≤ 0.038), glucose metabolism (all P ≤ 0.029), lipid profile (all P < 0.035), liver (all P ≤ 0.011), and pro-inflammatory biomarkers (all P ≤ 0.030). No associations of serum 25(OH)D concentrations were found with pro-inflammatory markers (all P ≥ 0.104), omega-6 and omega-3 oxylipins, nor eCBs concentrations or their analogs (all P ≥ 0.05). CONCLUSION: The present findings support the idea that 25(OH)D could be a useful predictor of CVD risk in young individuals.

Fumadores y riesgo de muerte hospitalaria por COVID calculado con el procesamiento de lenguaje natural de SAVANA en el ámbito de Castilla-La Mancha / Smokers and risk of hospital death by COVID calculated with SAVANA's natural language processing in the Castilla-La Mancha area

Introducción Durante la pandemia de COVID se especuló que los pacientes con el virus que tenían relación con el tabaco podrían tener una menor probabilidad de agravamiento de la enfermedad o muerte. Para evaluar si existe una asociación entre el tabaquismo y el riesgo de mortalidad intrahospitalaria se utiliza la tecnología de Big Data y Procesamiento del Lenguaje Natural (PLN) de SAVANA. Método Se llevó a cabo un estudio de cohortes retrospectivo, observacional y sin intervención basado en datos de vida real extraídos de registros médicos de toda Castilla-La Mancha utilizando las técnicas de PLN e inteligencia artificial desarrolladas por SAVANA. El estudio abarcó toda la población de esta Comunidad con historia clínica electrónica en SESCAM que presentara diagnóstico de COVID desde el 1 de marzo de 2020 al 28 de febrero de 2021. Resultados Los fumadores tienen mayor porcentaje de factores de riesgo cardiovascular (hipertensión arterial, dislipemia y diabetes), EPOC, asma, EPID, CI, ECV, TEP, cáncer en general y cáncer de pulmón en particular, bronquiectasias, insuficiencia cardíaca y antecedentes de neumonía, de forma significativa (p<0,0001). Los pacientes exfumadores, fumadores y no fumadores tienen una diferencia de edad significativa. En cuanto a las muertes hospitalarias, fueron más frecuentes en el caso de los exfumadores, siguiendo los fumadores y luego los no fumadores (p<0,0001). Conclusión Existe un mayor riesgo de mortalidad intrahospitalaria en los pacientes infectados por SARS-CoV-2 que sean fumadores activos o hayan fumado en el pasado. (AU)

Introduction During the COVID pandemic, it was speculated that patients with the virus who were smoking-related might have a lower likelihood of disease exacerbation or death. To assess whether there is an association between smoking and risk of in-hospital mortality, SAVANA's big data and natural language processing (NLP) technology is used. Method A retrospective, observational, non-interventional cohort study was conducted based on real-life data extracted from medical records throughout Castilla-La Mancha using natural language processing and artificial intelligence techniques developed by SAVANA. The study covered the entire population of this region with Electronic Medical Records in SESCAM presenting with a diagnosis of COVID from March 1, 2020 to February 28, 2021. Results Smokers had a significantly higher percentage of cardiovascular risk factors (hypertension, dyslipidemia and diabetes), COPD, asthma, IDP, IC, CVD, PTE, cancer in general and lung cancer in particular, bronchiectasis, heart failure and a history of pneumonia (P<.0001). Former smokers, current smokers and non-smokers have a significant age difference. As for in-hospital deaths, they were more frequent in the case of ex-smokers, followed by smokers and then non-smokers (P<.0001). Conclusion There is an increased risk of dying in hospital in SARS-CoV-2-infected patients who are active smokers or have smoked in the past. (AU)

High frequency of endoluminal thrombus in patients with ischaemic stroke following AARS-CoV-2 infection.

BACKGROUND: Ischaemic stroke may be a major complication of SARS-CoV-2 infection. Studying and characterising the different aetiological subtypes, clinical characteristics, and functional outcomes may be valuable in guiding patient selection for optimal management and treatment. METHODS: Data were collected retrospectively on consecutive patients with COVID-19 who developed acute focal brain ischaemia (between 1 March and 19 April 2020) at a tertiary university hospital in Madrid (Spain). RESULTS: During the study period, 1594 patients were diagnosed with COVID-19. We found 22 patients with ischaemic stroke (1.38%), 6 of whom did not meet the inclusion criteria. The remaining 16 patients were included in the study (15 cases of ischaemic stroke and one case of transient ischaemic attack). Median baseline National Institutes of Health Stroke Scale score was 9 (interquartile range: 16), and mean (standard deviation) age was 73 years (12.8). Twelve patients (75%) were men. Mean time from COVID-19 symptom onset to stroke onset was 13 days. Large vessel occlusion was identified in 12 patients (75%). We detected elevated levels of D-dimer in 87.5% of patients and C-reactive protein in 81.2%. The main aetiology was atherothrombotic stroke (9 patients, 56.3%), with the predominant subtype being endoluminal thrombus (5 patients, 31.2%), involving the internal carotid artery in 4 cases and the aortic arch in one. The mortality rate in our series was 44% (7 of 16 patients). CONCLUSIONS: In patients with COVID-19, the most frequent stroke aetiology was atherothrombosis, with a high proportion of endoluminal thrombus (31.2% of patients). Our clinical and laboratory data support COVID-19-associated coagulopathy as a relevant pathophysiological mechanism for ischaemic stroke in these patients.

Use of direct oral anticoagulants and low molecular weight heparin in venous thromboembolism associated with cancer: real-world evidence in Argentina.

BACKGROUND: Venous thromboembolism (VTE) and major bleeding (MB) are common in cancer patients. Reduced-doses of antithrombotics as secondary prophylaxis have limited data. This work aims to describe and to compare treatments and outcomes for cancer-associated VTE. RESEARCH DESIGN AND METHODS: Retrospective study. Adults with cancer-associated VTE were included. After 3-6 months of full-doses of anticoagulants, three strategies were considered: A) lowering the doses; B) maintaining full-doses; C) stopping treatment. The strategy and medication used were shown in a descriptive analysis and the rate of bleeding and VTE-recurrence between those in a comparative analysis. RESULTS: A total of 420 patients were included, 56.2% received DOACs, 43.8% enoxaparin. Strategy was defined in 257 patients: A (50.2%), B (46.3%), and C (3.5%). Forty-one (9.8%) had VTE-recurrence and 15 (3.6%) had MB or clinically relevant non-major bleeding (CRNMB).According to strategy, recurrent-VTE was 8.5% (A), 4.2% (B), and 11.1 (C) (p = 0.22), MB or CRNMB was 0.8% (A), 1.7% (B), and 0% (C) (p = 0.64). CONCLUSIONS: DOACs and strategy A were the most frequently used agent and strategy, respectively. There were no differences between medications or strategies used. The results must be interpreted with caution, and it is a retrospective single-center study, probably with information and selection bias.

Capsaicinoids and Their Effects on Cancer: The "Double-Edged Sword" Postulate from the Molecular Scale.

Capsaicinoids are a unique chemical species resulting from a particular biosynthesis pathway of hot chilies (Capsicum spp.) that gives rise to 22 analogous compounds, all of which are TRPV1 agonists and, therefore, responsible for the pungency of Capsicum fruits. In addition to their human consumption, numerous ethnopharmacological uses of chili have emerged throughout history. Today, more than 25 years of basic research accredit a multifaceted bioactivity mainly to capsaicin, highlighting its antitumor properties mediated by cytotoxicity and immunological adjuvancy against at least 74 varieties of cancer, while non-cancer cells tend to have greater tolerance. However, despite the progress regarding the understanding of its mechanisms of action, the benefit and safety of capsaicinoids' pharmacological use remain subjects of discussion, since CAP also promotes epithelial-mesenchymal transition, in an ambivalence that has been referred to as "the double-edge sword". Here, we update the comparative discussion of relevant reports about capsaicinoids' bioactivity in a plethora of experimental models of cancer in terms of selectivity, efficacy, and safety. Through an integration of the underlying mechanisms, as well as inherent aspects of cancer biology, we propose mechanistic models regarding the dichotomy of their effects. Finally, we discuss a selection of in vivo evidence concerning capsaicinoids' immunomodulatory properties against cancer.

Prostate cancer detection using e-nose and AI for high probability assessment.

This research aims to develop a diagnostic tool that can quickly and accurately detect prostate cancer using electronic nose technology and a neural network trained on a dataset of urine samples from patients diagnosed with both prostate cancer and benign prostatic hyperplasia, which incorporates a unique data redundancy method. By analyzing signals from these samples, we were able to significantly reduce the number of unnecessary biopsies and improve the classification method, resulting in a recall rate of 91% for detecting prostate cancer. The goal is to make this technology widely available for use in primary care centers, to allow for rapid and non-invasive diagnoses.