Evolution of pretransplant cardiac risk factor burden and major adverse cardiovascular events in liver transplant recipients over time.

Major adverse cardiovascular events (MACEs) are the leading cause of early (<1 y) complications after liver transplantation (LT). NASH, the leading indication for waitlisting for LT, is associated with high cardiac risk factor burden. The contemporary prevalence and temporal trends in pretransplant cardiac risk factor burden and post-LT MACE among LT recipients (LTRs) with and without NASH are unknown. The aim of this study was to evaluate (1) the evolution of post-LT cardiac risk factors in LTRs over time and (2) post-LT MACE over time, stratified by NASH status. This is a retrospective cohort of 1775 adult LTRs at a single transplant center (2003-2020). MACE was defined as death or hospitalization from myocardial infarction, revascularization, stroke, heart failure during the first post-LT year. Between 2003 and 2020, there was a significant increase in pre-LT NASH ( ptrend <0.05). There was also a significant increase in pre-LT obesity, atherosclerotic cardiovascular (CV) disease, and older age (≥65 y old) ( ptrend <0.05 for all). There was no significant change in the proportion of LTRs with diabetes, chronic kidney disease, or heart failure. Unexpectedly, there were no changes in the rate of post-LT MACE over the study period (-0.1% per year, ptrend =0.44). The lack of change in MACE despite an increase in CV risk factor prevalence may reflect advancement in the identification and management of CV risk factors in LTRs. With projected continued increase in cardiac risk burden and the proportion of patients transplanted for NASH, it is critical for LT programs to develop and implement quality improvement efforts to optimize CV care in LTRs.

Enhancing Giardicidal Activity and Aqueous Solubility through the Development of "RetroABZ", a Regioisomer of Albendazole: In Vitro, In Vivo, and In Silico Studies.

Parasitic diseases, including giardiasis caused by Giardia lamblia (G. lamblia), present a considerable global health burden. The limited effectiveness and adverse effects of current treatment options underscore the necessity for novel therapeutic compounds. In this study, we employed a rational design strategy to synthesize retroalbendazole (RetroABZ), aiming to address the limitations associated with albendazole, a commonly used drug for giardiasis treatment. RetroABZ exhibited enhanced in vitro activity against G. lamblia trophozoites, demonstrating nanomolar potency (IC50 = 83 nM), outperforming albendazole (189 nM). Moreover, our in vivo murine model of giardiasis displayed a strong correlation, supporting the efficacy of RetroABZ, which exhibited an eleven-fold increase in potency compared to albendazole, with median effective dose (ED50) values of 5 µg/kg and 55 µg/kg, respectively. A notable finding was RetroABZ's significantly improved water solubility (245.74 µg/mL), representing a 23-fold increase compared to albendazole, thereby offering potential opportunities for developing derivatives that effectively target invasive parasites. The molecular docking study revealed that RetroABZ displays an interaction profile with tubulin similar to albendazole, forming hydrogen bonds with Glu198 and Cys236 of the ß-tubulin. Additionally, molecular dynamics studies demonstrated that RetroABZ has a greater number of hydrophobic interactions with the binding site in the ß-tubulin, due to the orientation of the propylthio substituent. Consequently, RetroABZ exhibited a higher affinity compared to albendazole. Overall, our findings underscore RetroABZ's potential as a promising therapeutic candidate not only for giardiasis but also for other parasitic diseases.

Content and Quality of Information about Stroke in Wikipedia across Multiple Languages.

BACKGROUND: Given the high contribution of stroke to the global burden of disease, there is a need for good-quality information on Web platforms such as Wikipedia. AIMS: This study aimed to describe the quality of the Wikipedia articles on stroke written in different languages. METHODS: We studied the world's 30 most spoken languages. With the DISCERN score, we evaluated the quality of the information within the Wikipedia articles. Three investigators assessed each of the texts translated to English. We also registered the word count, the number of references, and if the text referred to the emergency status of stroke, cues to suspect a stroke, and allusions to endovascular treatment. RESULTS: There is a Wikipedia article for stroke in 23 out of the 30 languages. The mean DISCERN score was 35 29.9 ± 9.2. Overall quality ranged from 3/5 in 26.1% to 1/5 in 17.4%. Word count had a mean of 36 3,145.8 ± 3,048.9 words, and the texts included a mean of 43.1 ± 57.3 references; 69.6% of the articles referred to stroke as a medical emergency, 52.2% included awareness symptoms, and 34.8% included endovascular management among the stroke treatments. Three pages included steroids as part of the stroke treatment. The DISCERN score was not correlated with the number of speakers, but it was positively correlated with the number of references (r = 0.90, p < 0.001) and the number of words (r = 0.78, p < 0.001) in the articles. CONCLUSION: The analyzed Wikipedia articles do not contain relevant and up-to-date information to the general population. Further, the content varies widely across the different languages and is missing for some of them. The missing versions disproportionally affect millions of potential information seekers in undeveloped countries.

Virtual Screening of FDA-Approved Drugs against Triose Phosphate Isomerase from Entamoeba histolytica and Giardia lamblia Identifies Inhibitors of Their Trophozoite Growth Phase.

Infectious diseases caused by intestinal protozoan, such as Entamoeba histolytica (E. histolytica) and Giardia lamblia (G. lamblia) are a worldwide public health issue. They affect more than 70 million people every year. They colonize intestines causing primarily diarrhea; nevertheless, these infections can lead to more serious complications. The treatment of choice, metronidazole, is in doubt due to adverse effects and resistance. Therefore, there is a need for new compounds against these parasites. In this work, a structure-based virtual screening of FDA-approved drugs was performed to identify compounds with antiprotozoal activity. The glycolytic enzyme triosephosphate isomerase, present in both E. histolytica and G. lamblia, was used as the drug target. The compounds with the best average docking score on both structures were selected for the in vitro evaluation. Three compounds, chlorhexidine, tolcapone, and imatinib, were capable of inhibit growth on G. lamblia trophozoites (0.05-4.935 µg/mL), while folic acid showed activity against E. histolytica (0.186 µg/mL) and G. lamblia (5.342 µg/mL).

A Versatile Method for Depth Data Error Estimation in RGB-D Sensors.

We propose a versatile method for estimating the RMS error of depth data provided by generic 3D sensors with the capability of generating RGB and depth (D) data of the scene, i.e., the ones based on techniques such as structured light, time of flight and stereo. A common checkerboard is used, the corners are detected and two point clouds are created, one with the real coordinates of the pattern corners and one with the corner coordinates given by the device. After a registration of these two clouds, the RMS error is computed. Then, using curve fittings methods, an equation is obtained that generalizes the RMS error as a function of the distance between the sensor and the checkerboard pattern. The depth errors estimated by our method are compared to those estimated by state-of-the-art approaches, validating its accuracy and utility. This method can be used to rapidly estimate the quality of RGB-D sensors, facilitating robotics applications as SLAM and object recognition.

Differential Detection of Enterovirus and Herpes Simplex Virus in Cerebrospinal Fluid by Real-Time RT-PCR.

BACKGROUND: Enterovirus (EV) and herpes simplex virus 1 and 2 (HSV1 and HSV2) are the main etiologic agents of central nervous system infections. Early laboratory confirmation of these infections is performed by viral culture of the cerebrospinal fluid (CSF), or the detection of specific antibodies in serum (e.g., HSV). The sensitivity of viral culture ranges from 65 to 75%, with a recovery time varying from 3 to 10 days. Serological tests are faster and easy to carry out, but they exhibit cross-reactivity between HSV1 and HSV2. Although molecular techniques are more sensitive (sensitivity >95%), they are more expensive and highly susceptible to cross-contamination. METHODS: A real-time RT-PCR for the detection of EV, HSV1, and HSV2 was compared with end-point nested PCR. RESULTS: We tested 87 CSF samples of patients with a clinical diagnosis of viral meningitis or encephalitis. Fourteen samples were found to be positive by RT-PCR, but only 8 were positive by end-point PCR. The RT-PCR showed a specificity range of 94-100%, the negative predictive value was 100%, and the positive predictive value was 62, 100, and 28% for HSV1, HSV2, and EV, respectively. CONCLUSION: Real-time RT-PCR detected EV, HSV1, and HSV2 with a higher sensitivity and specificity than end-point nested RT-PCR.

Synthesis, in vitro and in vivo giardicidal activity of nitrothiazole-NSAID chimeras displaying broad antiprotozoal spectrum.

We designed and synthesized five new 5-nitrothiazole-NSAID chimeras as analogues of nitazoxanide, using a DCC-activated amidation. Compounds 1-5 were tested in vitro against a panel of five protozoa: 2 amitochondriates (Giardia intestinalis, Trichomonas vaginalis) and 3 kinetoplastids (Leishmania mexicana, Leishmania amazonensis and Trypanosoma cruzi). All chimeras showed broad spectrum and potent antiprotozoal activities, with IC50 values ranging from the low micromolar to nanomolar order. Compounds 1-5 were even more active than metronidazole and nitazoxanide, two marketed first-line drugs against giardiasis. In particular, compound 4 (an indomethacin hybrid) was one of the most potent of the series, inhibiting G. intestinalis growth in vitro with an IC50 of 0.145µM. Compound 4 was 38-times more potent than metronidazole and 8-times more active than nitazoxanide. The in vivo giardicidal effect of 4 was evaluated in a CD-1 mouse model obtaining a median effective dose of 1.709µg/kg (3.53nmol/kg), a 321-fold and 1015-fold increase in effectiveness after intragastric administration over metronidazole and nitazoxanide, respectively. Compounds 1 and 3 (hybrids of ibuprofen and clofibric acid), showed potent giardicidal activities in the in vitro as well as in the in vivo assays after oral administration. Therefore, compounds 1-5 constitute promising drug candidates for further testing in experimental chemotherapy against giardiasis, trichomoniasis, leishmaniasis and even trypanosomiasis infections.

Diagnosis and Management of Hereditary Hemochromatosis.

This JAMA Insights Clinical Review discusses the diagnosis and management of hereditary hemochromatosis, including clinical and laboratory characteristics, gene testing and interpretation, and the role of imaging and liver biopsy.

Race, substance use, and evaluation for heart transplantation: Insights from a large urban medical center.

It is unknown whether racial disparities in access to heart transplantation (HT) are amplified when coupled with substance use. We examined patients evaluated for HT over 8 years at an urban transplant center. We evaluated substance use and race/ethnicity as independent and interactive predictors of HT and left ventricular assist device (LVAD) implantation. Of 1,148 patients evaluated for HT, substance use was cited as an ineligibility factor in 151 (13%) patients, 16 (11%) of whom ultimately received HT. Significantly more non-Hispanic Black (NHB) patients were deemed ineligible due to substance use (n = 59, 19%) compared to other races/ethnicities (non-Hispanic white: n = 68, 12%; other race/ethnicity: n = 24, p = 0.002). No racial differences were observed in the likelihood of HT among patients initially excluded for substances, but more NHB patients ultimately received LVAD than the other racial groups. This study encourages greater awareness of the role of substance use and race in the HT evaluation.

[Guillain-Barré syndrome. Its association with alpha tumor necrosis factor]. / Síndrome de Guillain-Barré. Asociación con antagonista de FNT?

BACKGROUND: adalimumab, a human recombinant monoclonal antibody against tumoral necrosis factor alpha (TNFα), has been associated with central nervous system demyelinating diseases and peripheral neuropathic syndrome. The Guillain-Barré Syndrome (GBS) is one of them. CLINICAL CASE: we presented the case of a 65 year old woman, with diabetes mellitus and psoriasic arthritis, treated with adalimumab; after the fourth infusion, she developed paresthesia and mild weakness in lower limbs, these symptoms persisted three days after each infusion and each time remitted spontaneously; following the eight dose, presented a characteristic clinical picture of the GBS, confirmed with neurophysiological studies that showed an axonal motor-sensitive polyneuropathy. The treatment consisted in intravenous immunoglobulin, with good outcome. CONCLUSIONS: the synergy among cellular and humoral immune responses, against peripheral nerve antigens is responsible of immunopathogenesis related to GBS. The prolonged and intensified pathologic immune response induced by adalimumab, may be associated to the development of GBS.

The Evolution of Dignity: An Intervention Model to Engage and Retain HIV-Positive Black Women in Care.

The Black community is currently battling two pandemics, one is HIV, and the other is COVID-19. Similarly, as with HIV, COVID-19 has shone a spotlight on our healthcare system's structural failings and revealed the disproportionate impact on the Black community, particularly Black women. Black women accounted for the largest proportion of new HIV diagnoses (58 %) among all women in 2018 and represented about one-quarter of new HIV diagnoses among all Black Americans. Additionally, Black women's exposure to an abundance of misinformation about the COVID-19 infection resulted in an increased risk of complications and death from the COVID-19 virus compared to other racial and ethnic groups. Factors that increase HIV transmission risks for Black women include living in poverty, intimate partner violence, and stigma associated with HIV. Moreover, environmental, physical, cultural, financial, social, and psychological barriers are identified as unique challenges for this population's cohort. After being diagnosed with HIV, Black often were unable to access quality HIV care. Access and retention in care are tantamount to the overall well-being of women who are HIV positive. Frequently healthcare providers may attempt to engage and retain patients using only clinical measures. Our non-clinical intervention, The Evolution of Dignity, supports medical outcomes by creating a process that empowers women to motivate themselves toward improved health outcomes while ensuring their engagement and retention in care. Thus, by implementing our comprehensive intervention, all of the necessary elements contributing and promoting improved service utilization and medical adherence are integrated.

YML018C protein localizes to the vacuolar membrane independently of Atg27p.

The function of the budding yeast YML018C protein remains to be determined. High-throughput studies have reported that the YML018C protein localizes to the vacuolar membrane and physically interacts with the autophagy-related protein Atg27p. While this evidence suggests a potential role for this uncharacterized protein in the process of autophagy, the function of this putative interaction remains uncharacterized. In this micropublication, we report our finding that the localization of the YML018C protein to the vacuolar membrane does not require Atg27p.

ATG8 is conserved between Saccharomyces cerevisiae and psychrophilic, polar-collected fungi.

Autophagy is a conserved catabolic process by which eukaryotic cells respond to stress by targeting damaged or unneeded molecules or organelles for sequestration into specialized vesicles known as autophagosomes. Autophagosomes ultimately facilitate the digestion and recycling of their contents by fusing with the degradative organelle of the cell. Studies of the budding yeast Saccharomyces cerevisiae have revealed various types of stress that can regulate autophagy, including starvation and extreme temperatures. While autophagy has not yet been directly shown to confer the ability to survive extreme cold or freeze-thaw stress in yeast, upregulation of autophagy has been directly implicated in the ability of arctic insects to survive cold temperatures. We are interested in investigating the potential role of autophagy in polar habitat survival by cold-loving (psychrophilic) yeast like Mrakia blollopsis. To begin to examine the conservation of Atg machinery in polar-collected yeast, we focused on Atg8, a small, ubiquitin-like protein that plays an important role in autophagy. We report that Atg8 is conserved between S. cerevisiae and polar-collected yeast, using Atg8 from Mrakia blollopsis (strain TGK1-2) as an example. This study represents the first direct examination of autophagy machinery conservation across mesophilic and psychrophilic species of yeast.

A Clinical Prognostic Scoring System for Neurocysticercosis.

Objectives In patients with neurocysticercosis (NCC), an accurate risk prediction would allow a better therapeutic approach; however, there are currently no tools that can enhance the accuracy of risk prediction. We designed a prognostic scoring system to be used by neurologists and other physicians managing patients with NCC. Materials and Methods Using data from clinical records of patients from a third-level national reference center for neurological diseases, we assessed demographic, clinical, and tomographic variables among 293 patients diagnosed with NCC. Multivariable logistic regression analyses were used to develop a clinical prognostic scoring instrument. Patients with NCC were assessed for neurological impairment at 3 months after diagnosis. Statistical Analysis Score accuracy was assessed by receiver operating characteristic (ROC) curve analysis. The primary outcome was the presence of neurological impairment, resulting in disability according to self-report or caregiver reports; this outcome was assessed during follow-up visits at 3 ± 1 months after discharge. Results The most common symptoms at presentation were headache (67%) and seizure (63%). A six-item (total score from -4 to + 2) prognostic instrument was constructed on the basis of the presence of seizures/headache at presentation, a leukocyte count above 12x 109/dL, the presence of six to ten parasites, subarachnoid localization, and the use of anthelmintic drugs. Among 113 patients with negative scores, 79.6% developed neurological deficits. Among patients with scores of 1 to 2, 64.6% recovered completely, with an overall accuracy of prediction of 74.7% and area under the ROC curve = 0.722 (95% CI, 0.664-0.780, p < 0.0001). Conclusions The clinical prognostic scoring system for NCC described in this study is a new instrument for use in daily clinical practice. It is simple to administer, and it has a prognostic accuracy of 75%. Its use has the potential to improve the quality of care by guiding appropriate decision-making and early management of patients with NCC.

[Acute bilateral thalamic infarcts in a young man with patent foramen ovale]. / Infarto agudo talámico bilateral en paciente joven con foramen oval permeable.

BACKGROUND: Patent foramen ovale (PFO) has been associated with cryptogenic stroke in young patients. CLINICAL CASE: A 27-year-old man presented with acute confusional syndrome, altered language, bradypsychia and somnolence. Brain MRI showed symmetrical bilateral thalamic infarctions probably due to occlusion of Percheron's artery type 2b. Echocardiography showed patent foramen ovale. CONCLUSIONS: Cerebrovascular disease is a frequent cause of disability and even death in young patients, and thus its medical approach should be emphasized.

Cryopreservation and the Freeze-Thaw Stress Response in Yeast.

The ability of yeast to survive freezing and thawing is most frequently considered in the context of cryopreservation, a practical step in both industrial and research applications of these organisms. However, it also relates to an evolved ability to withstand freeze-thaw stress that is integrated with a larger network of survival responses. These responses vary between different strains and species of yeast according to the environments to which they are adapted, and the basis of this adaptation appears to be both conditioned and genetic in origin. This review article briefly touches upon common yeast cryopreservation methods and describes in detail what is known about the biochemical and genetic determinants of cell viability following freeze-thaw stress. While we focus on the budding yeast Saccharomyces cerevisiae, in which the freeze-thaw stress response is best understood, we also highlight the emerging diversity of yeast freeze-thaw responses as a manifestation of biodiversity among these organisms.

Effect of restraint stress on the population of intestinal intraepithelial lymphocytes in mice.

The impact of restraint stress on the intestinal immune system, particularly on intestinal intraepithelial lymphocytes (i-IEL), has not been described in detail. Thus, the purpose of this study was to assess the effects of restraint stress, including those produced by increases in glucocorticoids and catecholamines, on the population of i-IEL. Mice were exposed to 1 or 4h restraint stress for 4 day, and the number of IEL in the mucosa of the proximal small intestine was determined by immunohistochemistry. The effects of restraint were also analyzed in mice submitted to different procedures: adrenalectomy, chemical sympathectomy, and treatment with a glucocorticoid antagonist (RU486), dexamethasone, and epinephrine. The main findings were that: (1) chronic restraint-stress reduced the i-IEl population in the small intestine; (2) adrenalectomy, treatment with RU-486 and chemical sympathectomy decreased the number of gammadelta, CD4+ and CD8+ T cells in non-stressed groups; (3) dexamethasone reduced the number of gammadelta and CD8+ T cells, and (4) epinephrine reduced the number of gammadelta, CD4+ and CD8+ T cells. These results demonstrated that restraint stress decreased the number of i-IEL in the proximal small intestine of mice, mainly by the combined action of higher concentrations of catecholamines and glucocorticoids, and that lower concentrations of glucocorticoids and catecholamines in unstressed mice preserved the population of i-IEL.

Physical activity measured with wrist and ankle accelerometers: Age, gender, and BMI effects.

Physical activity (PA) is associated with various aspects of physical and mental health and varies by age and BMI. We aimed to compare PA measures obtained with wrist and ankle accelerometers and characterize their associations with age and BMI. We assessed PA mean and PA variability (indexed by coefficient of variation (CV)) at daytime and nighttime periods for seven consecutive days (M = 152.90 h) in 47 healthy participants (18-73 years old, 21 females). Diurnally, mean PA for both ankle and wrist and CV of PA for ankle decreased from the first to the second half of daytime (p < 0.05). There were no differences in mean PA between wrist and ankle at any time-period (p > 0.2). CV of ankle PA at daytime was significantly higher than wrist PA (p < .0001). The opposite pattern was observed at nighttime (p < .0001). Pearson correlation analyses were performed to assess the associations between wrist (or ankle) PA and age and BMI. Mean daytime (but not nighttime) activity for wrist and ankle decreased significantly with age (p < .05). PA variability also decreased with age for wrist and ankle during daytime and for ankle during nighttime (p < .05). BMI was negatively associated with wrist daytime PA variability (p < .05). There were no gender effects on activity measures. These findings indicate that wrist and ankle mean PA measures were not significantly different but were significantly different (p < 0.5) for PA variability in both daytime and nighttime. Age-related decreases of PA-mean and variability were observed during daytime in wrist and ankle, whereas higher wrist daytime variability was inversely associated with BMI. These findings provide new insights into PA features in free-living environment, which are relevant for public health and may have implications for clinical assessment of neurodegenerative disorders impacting PA and their interaction with demographics.

Intravenous Drug Use Is Novel Predictor of Infectious Intracranial Aneurysms in Patients with Infective Endocarditis.

INTRODUCTION: Infectious intracranial aneurysms (IIAs) are a rare but potentially devastating complication of infective endocarditis. The clinical and radiographic findings that predispose patients to IIA remain poorly understood. METHODS: We performed a retrospective review of a prospectively maintained database of consecutive endocarditis patients undergoing catheter-based angiography at a single tertiary-level academic center during the period of July 2013-December 2017. Patient records were reviewed for clinical and radiographic characteristics that may be associated with IIA. Multivariate regression models were used to evaluate the relationship between clinical and radiographic characteristics and presence of IIA on invasive imaging. RESULTS: Of 92 patients included in this analysis, 12 of them with 19 IIAs were discovered. Univariate analysis identified age, male sex, presence of hemorrhage, and history of IV drug use (IVDU) as predictors of IIA presence. After multivariate analysis, only intracranial hemorrhage and IVDU remained as independent predictors of IIA. CONCLUSIONS: Presence of hemorrhage on noninvasive imaging and history of IVDU are independently predictive of IIA presence in patients with infectious endocarditis. Risk stratification using these 2 factors may help identify the most vulnerable populations for IIA formation.

Comparison of Biological Properties of Two Medicinal Extracts of the Tehuacan-Cuicatlan Valley.

In the Valley of Tehuacan-Cuicatlan, Cyrtocarpa procera and Bursera morelensis are located and are used in traditional medicine. In this research, several biological properties were evaluated. The methanol extracts of C. procera (MeCp) and B. morelensis (MeBm) were obtained by maceration. The antibacterial activities of the extracts were evaluated by the Kirby-Baüer disc-diffusion method. The wound healing activity was evaluated by histopathological analysis. Both extracts had a bacteriostatic effect in the Staphylococcus aureus (MeCp MIC = 0.25 mg/mL and MeBm MIC = 1 mg/mL) and the Vibrio cholerae (MeCp MIC = 1 mg/mL and MeBm MIC = 4 mg/mL). Both extracts demonstrated a wound healing efficacy similar to the reference standard (Recoveron). They also showed a high antioxidant capacity (MeCp SC50 = 5.75 µg/mL and MeBm SC50 = 4.27 µg/mL). These results are related to the concentration of phenols (MeCp = 166 and MeBm = 236.6 mg GAe/g) and flavonoids of MeCp = 16 and MeBm = 22 µg Qe/g. Both extracts, acting in a similar way in microorganisms that cause infection thanks to their antioxidant activity, favor the healing of wounds. This is the first study in which the biological properties of these two species are compared.