Microporous water with high gas solubilities.

Liquids with permanent microporosity can absorb larger quantities of gas molecules than conventional solvents1, providing new opportunities for liquid-phase gas storage, transport and reactivity. Current approaches to designing porous liquids rely on sterically bulky solvent molecules or surface ligands and, thus, are not amenable to many important solvents, including water2-4. Here we report a generalizable thermodynamic strategy to preserve permanent microporosity and impart high gas solubilities to liquid water. Specifically, we show how the external and internal surface chemistry of microporous zeolite and metal-organic framework (MOF) nanocrystals can be tailored to promote the formation of stable dispersions in water while maintaining dry networks of micropores that are accessible to gas molecules. As a result of their permanent microporosity, these aqueous fluids can concentrate gases, including oxygen (O2) and carbon dioxide (CO2), to much higher densities than are found in typical aqueous environments. When these fluids are oxygenated, record-high capacities of O2 can be delivered to hypoxic red blood cells, highlighting one potential application of this new class of microporous liquids for physiological gas transport.

Structure and assembly of the mitochondrial membrane remodelling GTPase Mgm1.

Balanced fusion and fission are key for the proper function and physiology of mitochondria1,2. Remodelling of the mitochondrial inner membrane is mediated by the dynamin-like protein mitochondrial genome maintenance 1 (Mgm1) in fungi or the related protein optic atrophy 1 (OPA1) in animals3-5. Mgm1 is required for the preservation of mitochondrial DNA in yeast6, whereas mutations in the OPA1 gene in humans are a common cause of autosomal dominant optic atrophy-a genetic disorder that affects the optic nerve7,8. Mgm1 and OPA1 are present in mitochondria as a membrane-integral long form and a short form that is soluble in the intermembrane space. Yeast strains that express temperature-sensitive mutants of Mgm19,10 or mammalian cells that lack OPA1 display fragmented mitochondria11,12, which suggests that Mgm1 and OPA1 have an important role in inner-membrane fusion. Consistently, only the mitochondrial outer membrane-not the inner membrane-fuses in the absence of functional Mgm113. Mgm1 and OPA1 have also been shown to maintain proper cristae architecture10,14; for example, OPA1 prevents the release of pro-apoptotic factors by tightening crista junctions15. Finally, the short form of OPA1 localizes to mitochondrial constriction sites, where it presumably promotes mitochondrial fission16. How Mgm1 and OPA1 perform their diverse functions in membrane fusion, scission and cristae organization is at present unknown. Here we present crystal and electron cryo-tomography structures of Mgm1 from Chaetomium thermophilum. Mgm1 consists of a GTPase (G) domain, a bundle signalling element domain, a stalk, and a paddle domain that contains a membrane-binding site. Biochemical and cell-based experiments demonstrate that the Mgm1 stalk mediates the assembly of bent tetramers into helical filaments. Electron cryo-tomography studies of Mgm1-decorated lipid tubes and fluorescence microscopy experiments on reconstituted membrane tubes indicate how the tetramers assemble on positively or negatively curved membranes. Our findings convey how Mgm1 and OPA1 filaments dynamically remodel the mitochondrial inner membrane.

Microbiota-driven vaccination in soft ticks: Implications for survival, fitness and reproductive capabilities in Ornithodoros moubata.

The Ornithodoros moubata (Om) soft tick, a vector for diseases like tick-borne human relapsing fever and African swine fever, poses challenges to conventional control methods. With diminishing insecticide efficacy, harnessing the tick's microbiota through innovative approaches like microbiota-driven vaccination emerges as a promising strategy for sustainable and targeted disease control. This study investigated the intricate relationship between Pseudomonas, a keystone taxon in the Om microbiome, and its impact on tick fitness, microbiome structure and network dynamics. Utilizing in silico analyses and empirical vaccination experiments, the role of Pseudomonas within microbial networks in the tick midguts (MG) and salivary glands (SG) of Om was studied. Additionally, the consequences of anti-microbiota vaccines targeting Pseudomonas and Lactobacillus on tick fitness, microbiome diversity and community assembly were explored. The result of the study shows that in Om, Pseudomonas plays a central role in microbial networks, influencing keystone species despite being categorized as peripheral (interacting with 47 different taxa, 13 of which are keystone species). Anti-microbiota vaccination targeting Pseudomonas and Lactobacillus yields distinct effects on tick fitness, with Pseudomonas vaccination significantly impacting female tick survival, while Lactobacillus significantly reduced oviposition and fertility. Microbiome changes post-vaccination reveal diversity alterations, emphasizing the impact of vaccine choice. Community assembly dynamics and network robustness analyses highlight Pseudomonas' pivotal role, in influencing topological features and network resilience. The findings of the study provide comprehensive insights into the intricate dynamics of Om microbial networks and the potential of targeted microbiota-driven vaccines for tick control.

Volatile biomarkers of Gram-positive bacteria of clinical relevance as a tool for infection diagnosis.

AIM: Volatile organic compounds (VOCs) are being studied as potential biomarkers in many infections. Therefore, this study aimed to analyze the volatile profile of three Gram-positive bacteria of clinical relevance to identify potential volatile biomarkers that allow their differentiation. METHODS AND RESULTS: L. monocytogenes, S. aureus, and E. faecalis clinical isolates were inoculated in a thioglycollate medium until grown. Then, VOCs were extracted by solid-phase microextraction, and the data obtained were subjected to multivariate analysis. According to our results, there was a high production of aldehydes in E. faecalis. In the case of alcohols, they only increased in L. monocytogenes, while ketones were produced significantly in all three bacteria, mainly due to acetoin. Acids were produced significantly in E. faecalis and L. monocytogenes. CONCLUSIONS: Potential biomarkers of L. monocytogenes could be 1-butanol and 2-methylbutanoic acid. In the case of E. faecalis, the VOC most related to its presence was nonanal. Lastly, potential biomarkers of S. aureus could be isoamyl butanoate and methionol, although some pyrazines have also been associated with this bacterium. SIGNIFICANCE AND IMPACT OF THE STUDY: The identification of potential biomarkers of these clinically relevant bacteria could open the way for the diagnosis of these infections through the analysis of volatile compounds.

Biological Effects of New Chemical-Mechanical Caries Removal Products on Human Dental Pulp Stem Cells.

INTRODUCTION: The aim of this study was to compare the biological effects of four chemical caries removal materials and to assess their cytotoxicity using human dental pulp stem cells (hDPSCs). METHODS: The products evaluated are: 1 - papain-based product (BRIX 3000®); 2 - papain/chloramine based products (NATURAL-CARE and Papacárie Duo®); and 3 - chloramine based product (Cariesolut). The following in vitro experiments were carried out: IC50 measurement, cell metabolic activity (MTT) assay, cell migration, immunofluorescence experiment, cell apoptosis analysis, and reactive oxygen species (ROS) production analysis. Statistical analyses were performed using one-way ANOVA followed by Tukey's post hoc test (p < 0.05). RESULTS: The IC50 values were: Brix 3000: 0.596%; Papacárie Duo: 0.052%; NATURAL CARE: 1.034%; and Cariesolut: 0.020%. The MTT assays showed non-adequate cell viability of all chemical-mechanical caries removal tested at 2% at 24, 48, and 72 h (p < 0.001). The same behaviour was observed at 0.1% in the Papacárie Duo and Cariesolut groups. In contrast, 0.1% of Brix 3000 at all times and NATURAL CARE at 24 h treated cells showed cell viability rates similar to the control group. At 0.01% only Brix 3000 did not show statistically significant differences at any time. Delayed cell migration was observed in all hDPSCs treated with Papacárie Duo and Cariesolut (p < 0.01 and p < 0.001). Phalloidin staining images showed a high confluence of cells in the presence of NATURAL CARE, similar to the control group. On the contrary, no cells were observed in Brix 3000 and Cariesolut at 2% and 0.1% concentrations. Papacárie Duo showed cells at all concentrations, but hDPSCs treated at 0.01% concentration exhibited better proliferation and spreading than those in the control group. Apoptosis essay showed that Brix 3000 at both 0.1% and 0.01% had a percentage of live cells higher than 99%, with 68.4% live cells at 2%, 3.69% early apoptotic cells, and 27.9% late apoptotic cells. Conversely, the rest of the materials showed an abundance of apoptotic cells, even at low concentrations. 0.1% and 0.01% of BRIX 3000 did not affect the ROS production levels, while 2% of BRIX 3000 counterpart very significantly increased the percentage of CM-H2DCFDA positive cells. Again, all concentrations of Cariesolut showed significantly higher levels of ROS production than those observed in control cells. CONCLUSION: Our results suggest that Brix 3000 would be the most suitable material for chemical caries removal, with Papacárie Duo and NATURAL CARE also being good options, and discourage the use of Cariesolut due to its low cytocompatibility on dental pulp stem cells.

Quality of life in patients undergoing minimally invasive surgery.

OBJECTIVE: Current evidence has shown how laparoscopic surgery results in shorter hospital stay, faster recovery, and better aesthetic results. However, we do not have information on populations in Latin America and the impact that the social environment has on quality of life in patients with gynecological cancer undergoing minimally invasive surgery. To assess quality of life of patients undergoing minimally invasive surgery in a gynecologic oncology department over time and to establish the relationship with patient and treatment variables. METHODS: This cross-sectional study evaluated the quality of life of women undergoing minimally invasive surgery from August 2019 to July 2021. The FACT-G (Functional Assessment of Cancer Therapy-General) scale encompasses global quality of life and four domains of physical, social, emotional, and functional components. This scale was applied to measure quality of life in the preoperative, early operative, and late postoperative periods. Additionally, mixed models were used to compare quality of life based on demographic and clinical factors after minimally invasive surgery. RESULTS: A total of 158 patients were analyzed. Belonging to a higher socioeconomic stratum (3 vs 1) had a positive impact on the global quality of life in patients undergoing surgery with an increase of 7.6 points (p=0.011). Also, a lower Charlson Index had a positive impact of 0.393 points for the physical component of quality of life (p=0.031). For the social component of quality of life, having a partner and being part of a higher socioeconomic stratum (3 and 2 vs 1) resulted in an increase of 2.11 (p=0.005), 4.06 (p<0.05), and 2.55 (p=0.004) points, respectively. Belonging to a higher socioeconomic stratum (3 vs 1) resulted in an increase of 2.03 points (p=0.031) for the functional component of quality of life. Finally, the complexity of the procedure, or whether the procedure was ambulatory or not did not impact quality of life. CONCLUSIONS: Lower Charlson Index, having a partner, or having higher socioeconomic status are all associated with higher quality of life of patients undergoing minimally invasive surgery.

Identification of volatile biomarkers of Trichomonas vaginalis infection in vaginal discharge and urine.

Trichomoniasis, a disease caused by Trichomonas vaginalis, is the most common non-viral sexually transmitted infection worldwide. The importance of its diagnosis lies in its ease of transmission and the absence of symptoms in most cases, as occurs in men, which have a significant role as asymptomatic carriers. The most widely used diagnostic methods are the fresh examination of vaginal or urethral secretions and molecular techniques. However, as they have some disadvantages and, sometimes, low sensitivity, new trichomoniasis diagnostic methods are necessary. Volatile organic compounds in clinical samples are effective in the diagnosis of different diseases. This work aimed to study, for the first time, those present in vaginal discharge and urine of patients with Trichomonas vaginalis infection to look for volatile biomarkers. The results showed that volatile compounds such as 2-methyl-1-propanol and cyclohexanone could serve as biomarkers in vaginal discharge samples, as well as 2-octen-1-ol and 3-nonanone in urine. Moreover, 3-hydroxy-2,4,4-trimethylpentyl 2-methylpropanoate found in vaginal discharge, highly correlated to positive patients, is also highly related to urines of patients with trichomoniasis. The biomarkers described in this study might be a promising diagnostic tool. KEY POINTS: • The incidence of Trichomonas vaginalis infection is increasing • Trichomonas vaginalis VOC study in vaginal discharge and urine was performed • The identification of volatile biomarkers could allow a new diagnostic method.

Feasibility of using volatile urine fingerprints for the differentiation of sexually transmitted infections.

Sexually transmitted infections (STIs) are a public health problem worldwide, and current diagnostic methods have certain limitations. In recent years, volatile organic compounds (VOCs) have been studied as an alternative diagnostic method. Due to this, this study aimed to detect, in vaginal swabs and urine samples, VOCs emitted by highly prevalent STIs-causing bacteria (Chlamydia trachomatis, Mycoplasma genitalium, and Neisseria gonorrhoeae) to identify potential biomarkers that allow the detection of these STIs. VOCs detected in urine samples showed a better differentiation of patients with STIs due to C. trachomatis from those not infected, with 2,6-dimethyl-4-heptanone as the volatile compound most related to the presence of this bacterium. Among the VOCs most related to M. genitalium in urine, 4-methyltetradecane and 2-methylpentadecane stood out, while 3,4,4-trimethyl-2-cyclohexen-1-one was the VOC most closely related to N. gonorrhoeae infection. Moreover, C12 alcohols were the main VOC family associated with positive samples in all three bacteria, which could indicate the presence of aldehyde reductases in their metabolism. In contrast, alcohols such as 3-methyl-1-heptanol and 1-octanol, as well as dimethyl esters, were more associated with negative samples and may be useful in ruling out an STI caused by one of these three bacteria. In short, the VOCs identified as potential biomarkers in patients with infection by C. trachomatis, M. genitalium, or N. gonorrhoeae could be used in the early diagnosis of these STIs, quickly interrupting the chain of transmission, especially interesting in asymptomatic patients. KEY POINTS: • Sexually transmitted infections are a serious public health problem worldwide. • The study of VOCs in multiple infections is increasing in recent years. • The identification of volatile biomarkers could allow new diagnostic methods.

Evaluation of the Premier Hb9210 instrument for HbA1c determination.

Background: Glycated hemoglobin measurements are a valuable tool for long-term blood glucose monitoring and the diagnosis of diabetes. Its widespread use has been made possible due to the development of new analytical methods with improved performances and standardization with reference materials. The aim of the present study was to evaluate the Trinity Biotech Premier Hb9210 analyzer for the measurement of HbA1c.Methods: The precision was assessed using the CLSI EP-15A3 and EP-10A3 protocols. The latter was also used to investigate linearity, carryover, and linear drift. The comparison study was performed between Premier Hb910 and Tosoh HLC-723 G8 through Passing-Bablok regression and the Bland-Altman plot. The Fleiss Kappa index was used to assess the degree of agreement. The interference of Hb variants was investigated using samples with Hb variants S, C, D, E, J, and Seville.Results: Within-run and between-run imprecision fell between 0.37% and 1.16%. No statistically significant nonlinearity, carry-over, and/or drift were observed. The resulting regression line of the Passing-Bablok analysis was y = 0.00 + 1.00x. The Pearson correlation coefficient was 0.997. In the Bland-Altman plot, the relative bias was 0.01%. The overall Fleiss Kappa index was 0.9. No interference from hemoglobin variants was observed.Conclusion: The Premier Hb9210 demonstrated a high degree of automation, reproducibility, good agreement, minimal carry-over effect, and excellent linearity across the wide range of HbA1c levels commonly found in diabetic patients and was not influenced by Hb variants.

Premier Hb9210 can be used as an alternative to monitor glycemic status.Premier Hb9210 is not affected by common hemoglobin variants.Premier Hb9210 can correctly classify diabetic patients.

Evaluation of the Congenital Hypothyroidism Detection Strategy in Extremely Preterm Infants in Western Andalusia.

OBJECTIVE: This study aimed to identify extremely premature infants (< 31 weeks of gestation and/or <1,500 g) affected by congenital hypothyroidism (CH) with delayed elevation of thyrotropin (TSH) and to evaluate the detection strategy for this pathology in our reference screening population. STUDY DESIGN: A descriptive and retrospective study was carried out with samples collected from western Andalusia and the autonomous city of Ceuta. RESULTS: This protocol allowed us to detect six neonates with delayed TSH elevation. One of them, due to serious heart problems, died without being able to confirm CH. In two neonates, however, it was possible to detect CH, another two presented a persistent TSH elevation but normal free T4, and another one presented a temporary TSH elevation. CONCLUSION: It is essential to repeat the CH screening in extremely premature infants, not only at the age of 15 days but also with a third sample at the moment of hospital discharge to detect cases with delayed TSH elevation. KEY POINTS: · The Newborn Screening Programs are an essential activity of preventive medicine.. · Extremely preterm infants have a very high risk of CH.. · Optimal management of thyroid dysfunction in this population remains to be established..

Biological properties of Ceraputty as a retrograde filling material: an in vitro study on hPDLSCs.

OBJECTIVES: To assess the cytocompatibility and bioactive potential of the new calcium silicate-based cement Ceraputty on human periodontal ligament stem cells (hPDLSCs) compared to Biodentine and Endosequence BC root repair material (ERRM). MATERIALS AND METHODS: hPDLSCs were isolated from extracted third molars from healthy donors. Standardized sample discs and 1:1, 1:2, and 1:4 eluates of the tested materials were prepared. The following assays were performed: surface element distribution via SEM-EDX, cell attachment and morphology via SEM, cell viability via a MTT assay, osteo/cemento/odontogenic marker expression via RT-qPCR, and cell calcified nodule formation via Alizarin Red S staining. hPDLSCs cultured in unconditioned or osteogenic media were used as negative and positive control groups, respectively. Statistical analysis was performed using one-way ANOVA or two-way ANOVA and Tukey's post hoc test. Statistical significance was established at p < 0.05. RESULTS: The highest Ca2+ peak was detected from Biodentine samples, followed by ERRM and Ceraputty. hPDLSC viability was significantly reduced in Ceraputty samples (p < 0.001), while 1:2 and 1:4 Biodentine and ERRM samples similar results to that of the negative control (p > 0.05). Biodentine and ERRM exhibited an upregulation of at least one cemento/odonto/osteogenic marker compared to the negative and positive control groups. Cells cultured with Biodentine produced a significantly higher calcified nodule formation than ERRM and Ceraputty (p < 0.001), which were also higher than the control groups (p < 0.001). CONCLUSION: Ceraputty evidenced a reduced cytocompatibility towards hPDLSCs on its lowest dilutions compared to the other tested cements and the control group. Biodentine and ERRM promoted a significantly higher mineralization and osteo/cementogenic marker expression on hPDLSCs compared with Ceraputty. Further studies are necessary to verify the biological properties of this new material and its adequacy as a retrograde filling material. CLINICAL RELEVANCE: This is the first study to elucidate the adequate biological properties of Ceraputty for its use as a retrograde filling material.

Experimental and Theoretical Studies on Acid Corrosion Inhibition of API 5L X70 Steel with Novel 1-N-α-d-Glucopyranosyl-1H-1,2,3-Triazole Xanthines.

A series of novel 1-N-α-d-glucopyranosyl-1H-1,2,3-triazole xanthines was synthesized from azido sugars (glucose, galactose, and lactose) and propargyl xanthines (theophylline and theobromine) using a typical copper (I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition. The corrosion inhibition activities of these new carbohydrate-xanthine compounds were evaluated by studying the corrosion of API 5 L X70 steel in a 1 M HCl medium. The results showed that, at 10 ppm, a 90% inhibition efficiency was reached by electrochemical impedance spectroscopy. The inhibitory efficiency of these molecules is explained by means of quantum chemical calculations of the protonated species with the solvent effect, which seems to better represent the actual situation of the experimental conditions. Some quantum chemical parameters were analyzed to characterize the inhibition performance of the tested molecules.

A practical access for fluoroscopically-guided percutaneous sacroplasty: Case report.

BACKGROUND: Sacral metastases represent the lowest percentage of invasion to the spine, however, as chemotherapy treatments progress, the cancer survival rate has become higher, and the percentage of sacral metastases has increased. Treatment options for sacrum metastases are surgery, radiotherapy, and minimally invasive techniques such as sacroplasty and radiofrequency ablation. Knowing the repercussions that advancing the needle anteriorly (viscera) or medially (sacral roots) can have during the sacroplasty we are describing a technique to perform c-arm sacroplasty in coaxial vision, to identify the anterior sacral cortical bone that is in the limits of the pelvic viscera as well as the sacral foraminal line. CASE PRESENTATION: In the current report, we present a 75-year-old male patient with prostate cancer metastatic to S1, S2, S3 and iliac, with severe lumbar axial pain VAS 8/10. With a caudal tilt between 35-45 degrees until aligning the sacrum in a coaxial view, a 11-gauge Jamshidi needle is advanced from s3 to s1. The trajectory of the needle during the procedure is corroborated in AP and lateral, S1 is cemented, and the needle is withdrawn to cement S2 and S3. After the sacroplasty with the coaxial access, the patient reported VAS 1-2/10. CONCLUSIONS: It is important to offer an adequate quality of life to patients with sacral fractures, whether associated with cancer or sacral insufficiency fractures (SIF). Sacroplasty, being a recently described technique, can be a very viable option for these patients, that's why it is important to have safe and reliable techniques to complement the approach of this minimally invasive technique.The coaxial access may be a safe and practical way to perform sacroplasty in these patients.

Efficacy and Safety of Celiac Plexus Neurolysis in the Treatment of Chronic Pain Secondary to Oncological Pathology of the Upper Hemiabdomen: A Systematic Review and Meta-Analysis.

Objectives: The management of chronic pain among patients with abdominal cancer is complex; against that, the neurolysis of the celiac plexus (CPN) is the best technique at the moment to determine the efficacy and safety in the treatment of chronic pain secondary to oncological pathology of the upper abdomen. Material and Methods: This was a systematic review of controlled clinical trials between 2000 and 2021, in the sources MEDLINE/PubMed, Cochrane, Scopus, Web of Science, and Google Scholar. Three independent evaluators analysed the results of the bibliographical research. The quality of the studies was assessed with the Jadad scale and the mean difference (95% confidence interval) and heterogeneity of the studies (I2) were calculated with Review Manager 5.3. Results: Seven hundred and forty-four publications were identified, including 13 studies in the qualitative synthesis and three studies in the quantitative synthesis. No difference was found in the decrease in pain intensity between 1 and 12 weeks after the intervention, comparing the experimental group with the control (P > 0.05). The adverse effects related to neurolysis were not serious and transitory, mentioning the most frequent adverse effects and reporting a percentage between 21% and 67% (with 17% for echoendoscopic neurolysis and 49% for percutaneous neurolysis). Conclusion: Celiac plexus neurolysis for the treatment of severe chronic pain secondary to oncological pathology in the upper hemiabdomen produces similar pain relief as conventional pharmacological analgesic treatment. It is a safe analgesic technique since the complications are mild and transitory.

The Use of Corticosteroids or Tocilizumab in COVID-19 Based on Inflammatory Markers.

BACKGROUND: The inflammatory cascade is the main cause of death in COVID-19 patients. Corticosteroids (CS) and tocilizumab (TCZ) are available to treat this escalation but which patients to administer it remains undefined. OBJECTIVE: We aimed to evaluate the efficacy of immunosuppressive/anti-inflammatory therapy in COVID-19, based on the degree of inflammation. DESIGN: A retrospective cohort study with data on patients collected and followed up from March 1st, 2020, to May 1st, 2021, from the nationwide Spanish SEMI-COVID-19 Registry. Patients under treatment with CS vs. those under CS plus TCZ were compared. Effectiveness was explored in 3 risk categories (low, intermediate, high) based on lymphocyte count, C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, and D-dimer values. PATIENTS: A total of 21,962 patients were included in the Registry by May 2021. Of these, 5940 met the inclusion criteria for the present study (5332 were treated with CS and 608 with CS plus TCZ). MAIN MEASURES: The primary outcome of the study was in-hospital mortality. Secondary outcomes were the composite variable of in-hospital mortality, requirement for high-flow nasal cannula (HFNC), non-invasive mechanical ventilation (NIMV), invasive mechanical ventilation (IMV), or intensive care unit (ICU) admission. KEY RESULTS: A total of 5940 met the inclusion criteria for the present study (5332 were treated with CS and 608 with CS plus TCZ). No significant differences were observed in either the low/intermediate-risk category (1.5% vs. 7.4%, p=0.175) or the high-risk category (23.1% vs. 20%, p=0.223) after propensity score matching. A statistically significant lower mortality was observed in the very high-risk category (31.9% vs. 23.9%, p=0.049). CONCLUSIONS: The prescription of CS alone or in combination with TCZ should be based on the degrees of inflammation and reserve the CS plus TCZ combination for patients at high and especially very high risk.

Erythropoietin in Spinocerebellar Ataxia Type 2: Feasibility and Proof-of-Principle Issues from a Randomized Controlled Study.

BACKGROUND: Several pieces of evidence have shown the neurotrophic effect of erythropoietin (EPO) and its introduction in the therapeutic practice of neurological diseases. However, its usefulness in the treatment of spinocerebellar ataxia type 2 (SCA2) has not been proven despite the fact that it is endogenously reduced in these patients. OBJECTIVE: The study aims to investigate the safety, tolerability, and clinical effects of a nasally administered recombinant EPO in SCA2 patients. METHODS: Thirty-four patients were enrolled in this double-blind, randomized, placebo-controlled, phase I-II clinical trial of the nasally administered human-recombinant EPO (NeuroEPO) for 6 months. The primary outcome was the change in the spinocerebellar ataxia functional index (SCAFI), while other motor, neuropsychological, and oculomotor measures were assessed. RESULTS: The 6-month changes in SCAFI score were slightly higher in the patients allocated to NeuroEPO treatment than placebo in spite of the important placebo effect observed for this parameter. However, saccade latency was significantly decreased in the NeuroEPO group but not in placebo. The frequency and severity of adverse events were similar between both groups, without evidences of hematopoietic activity of the drug. CONCLUSIONS: This study demonstrated the safety and tolerability of NeuroEPO in SCA2 patients after 6 months of treatments and suggested a small clinical effect of this drug on motor and cognitive abnormalities, but confirmatory studies are warranted. © 2022 International Parkinson and Movement Disorder Society.

Dialysis Outcomes in a Middle-Income Country: An Updated Comparison of Patient Mortality between Hemodialysis and Peritoneal Dialysis.

INTRODUCTION: Comparisons of survival between dialysis modalities is of great importance to patients with kidney failure, their families, and healthcare systems. OBJECTIVE: This study's objective was to compare mortality of patients on chronic hemodialysis (HD) or peritoneal dialysis (PD) and identify variables associated with mortality. METHODS: This retrospective cohort study included adult incident patients with kidney failure treated with HD or PD by the Baxter Renal Care Services network in Colombia. The study was conducted between January 1, 2008, and December 31, 2013 (recruitment period), with follow-up until December 31, 2018. The outcome was the cumulative mortality rate at 1, 2, 3, 4, and 5 years. Propensity score matching (PSM) and the Gompertz parametric survival model were used to compare mortality in HD versus PD. RESULTS: The analysis included 12,499 patients, of whom 57.4% were on PD at inception. The overall mortality rate was 14.0 events per 100 patient-years (95% confidence interval [CI], 13.61-14.42). Using an intention-to-treat approach, crude mortality rates were significantly lower in patients receiving HD (HD: 12.3 deaths per 100 patient-years [95% CI, 11.7-12.8] vs. PD: 15.5 [14.9-16.1], p < 0.01). Using a Gompertz parametric survival model, dialysis modality was not significantly associated with mortality (hazard ratio HD vs. PD 1.0, 95% CI, 0.9-1.1). After PSM, the mortality cumulative incidence functions between HD and PD were not statistically significantly different (p = 0.88). CONCLUSIONS: The present study in a large cohort of incident dialysis patients with at least 5 years follow-up and using PSM methods showed no differences in cumulative mortality between HD and PD patients. This evidence from a middle-income country may facilitate the process of dialysis modality selection globally.

Latinx adolescent migrant challenges in reuniting with family members.

Family reunification occurs when migrants relocate without intact family units, and later reunite in new countries. Family serial migration and reunification is a global issue, relating to both voluntary and involuntary migrants who seek physical safety, psychological well-being, and economic self-sufficiency in new countries. Early studies alluded to a joyful family reconsolidation, while recent studies have found stressful reunions. This study provides an overview of the family reunification process of Latinx adolescents who have migrated to join their families in the United States (U.S.). The study conducted detailed interviews of 20 Latinx adolescents, aged 12-18 years old, in order to provide an in-depth examination of their pre and postmigration experiences. The results reveal three phases of family reunification: Latinx adolescents' experiences after their parent(s) left to migrate to the U.S.; their own migration journey to the U.S.; and their family reunification, adaptation, and adjustment to the U.S. The findings suggest that it is essential for mental health professionals to understand and acknowledge the multiple psychosocial challenges of Latinx adolescents' reuniting with their families in a new country. This includes feelings of abandonment and grief after their parent(s) departure to the U.S., their own migration journey to the U.S. which may have been experienced as traumatic, and psychosocial challenges in adjustment and adaptation in the U.S. after family reunification.

Towards Developing a Robust Intrusion Detection Model Using Hadoop-Spark and Data Augmentation for IoT Networks.

In recent years, anomaly detection and machine learning for intrusion detection systems have been used to detect anomalies on Internet of Things networks. These systems rely on machine and deep learning to improve the detection accuracy. However, the robustness of the model depends on the number of datasamples available, quality of the data, and the distribution of the data classes. In the present paper, we focused specifically on the amount of data and class imbalanced since both parameters are key in IoT due to the fact that network traffic is increasing exponentially. For this reason, we propose a framework that uses a big data methodology with Hadoop-Spark to train and test multi-class and binary classification with one-vs-rest strategy for intrusion detection using the entire BoT IoT dataset. Thus, we evaluate all the algorithms available in Hadoop-Spark in terms of accuracy and processing time. In addition, since the BoT IoT dataset used is highly imbalanced, we also improve the accuracy for detecting minority classes by generating more datasamples using a Conditional Tabular Generative Adversarial Network (CTGAN). In general, our proposed model outperforms other published models including our previous model. Using our proposed methodology, the F1-score of one of the minority class, i.e., Theft attack was improved from 42% to 99%.

Fecal Volatile Organic Compounds and Microbiota Associated with the Progression of Cognitive Impairment in Alzheimer's Disease.

Metabolites produced by an altered gut microbiota might mediate the effects in the brain. Among metabolites, the fecal volatile organic compounds (VOCs) are considered to be potential biomarkers. In this study, we examined both the VOCs and bacterial taxa in the feces from healthy subjects and Alzheimer's disease (AD) patients at early and middle stages. Remarkably, 29 fecal VOCs and 13 bacterial genera were differentiated from the healthy subjects and the AD patients. In general, higher amounts of acids and esters were found in in the feces of the AD patients and terpenes, sulfur compounds and aldehydes in the healthy subjects. At the early stage of AD, the most relevant VOCs with a higher abundance were short-chain fatty acids and their producing bacteria, Faecalibacterium and Lachnoclostridium. Coinciding with the development of dementia in the AD patients, parallel rises of heptanoic acid and Peptococcus were observed. At a more advanced stage of AD, the microbiota and volatiles shifted towards a profile in the feces with increases in hexanoic acid, Ruminococcus and Blautia. The most remarkable VOCs that were associated with the healthy subjects were 4-ethyl-phenol and dodecanol, together with their possible producers Clostridium and Coprococcus. Our results revealed a VOCs and microbiota crosstalk in AD development and their profiles in the feces were specific depending on the stage of AD. Additionally, some of the most significant fecal VOCs identified in our study could be used as potential biomarkers for the initiation and progression of AD.