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Objective: Chagas disease (CD) globalization facilitated the co-infection with Human Immunodeficiency Virus (HIV) in endemic and non-endemic areas. Considering the underestimation of Trypanosoma cruzi (T. cruzi)-HIV co-infection and the risk of life-threatening Chagas Disease Reactivation (CDR), this study aimed to analyze the major co-infection clinical characteristics and its mortality rates., Methods: This is a cross-sectional retrospective multicenter study of patients with CD confirmed by two serological or one parasitological tests, and HIV infection confirmed by immunoblot. CDR was diagnosed by direct microscopy with detection of trypomastigote forms in the blood or other biological fluids and/or amastigote forms in inflammatory lesions., Results: Out of 241 patients with co-infection, 86.7% were from Brazil, 47.5% had <200 CD4+ T cells/μL and median viral load was 17,000 copies/μL. Sixty CDR cases were observed. Death was more frequent in patients with reactivation and was mainly caused by CDR. Other causes of death unrelated to CDR were the manifestation of opportunistic infections in those with Acquired Immunodeficiency Syndrome. The time between the co-infection diagnosis to death was shorter in patients with CDR. Lower CD4+ cells count at co-infection diagnosis was independently associated with reactivation. Similarly, lower CD4+ cells numbers at co-infection diagnosis and male sex were associated with higher lethality in CDR. Additionally, CD4+ cells were lower in meningoencephalitis than in myocarditis and milder forms., Conclusion: This study showed major features on T. cruzi-HIV co-infection and highlighted the prognostic role of CD4+ cells for reactivation and mortality. Since lethality was high in meningoencephalitis and all untreated patients died shortly after the diagnosis, early diagnosis, immediate antiparasitic treatment, patient follow-up and epidemiological surveillance are essentials in T. cruzi/HIV co-infection and CDR managements., Competing Interests: The authors have declared that no competing interests exist.

Background: Muscle weakness and exercise intolerance contribute to reduced quality of life (QOL) in Barth syndrome (BTHS). Our group previously found that 12 weeks of resistance exercise training (RET) improved muscle strength, however, did not increase muscle (lean) mass or QOL in n = 3 young adults with BTHS. The overall objective of this pilot study was to examine the safety and effectiveness of RET plus daily protein supplementation (RET + protein) on muscle strength, skeletal muscle mass, exercise tolerance, cardiac function, and QOL in late adolescents/young adults with BTHS., Methods: Participants with BTHS (n = 5, age 27 ± 7) performed 12 weeks of supervised RET (60 minutes per session, three sessions/week) and consumed 42 g/day of whey protein. Muscle strength, muscle mass, exercise capacity, cardiac function, and health-related QOL were assessed pre-post intervention., Results: RET + protein was safe, increased muscle strength and quality of life, and tended to increase lean mass., Conclusions: RET + protein appears safe, increases muscle strength and quality of life and tends to increase lean mass. Larger studies are needed to confirm these findings and to fully determine the effects of RET + protein in individuals with BTHS., Competing Interests: All authors declare that they have no conflict of interest., (© 2021 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)

139La nuclear quadrupole resonance and spin-lattice relaxation techniques are used to compute static magnetic features of magnetic susceptibility in Zn2+-substituted La2Cu1-xZnxO4 compounds. Sublattice magnetization depends on x value and temperature depends on changes in pure La2CuO4 compounds. Relaxation rates are associated with spin wave alterations and correlation length decreases in the compounds.

35Cl nuclear-magnetic-resonance and relaxation techniques measure magnetic ordering as functions of tetragonal axis and external magnetic field orientation in Sr2CuO2Cl2 single crystals. A temperature and magnetic field-dependent anisotropic broadening of NMR spectral lines occurs without a paramagnetic shift due to the nonzero thermal average moment of Cu2+ in the a-b plane of the crystals.

Experts from the University of Milan have been investigating Forni Glacier in the Italian alps for decades, resulting in the archive of a cumbersome mass of observed data. While the analysis of archive maps, medium resolution satellite images and DEM's may provide an overview of the long-term processes, the application of close-range sensing techniques offers the unprecedented opportunity to operate a 4D reconstruction of the glacier geometry at both global and local levels. In the latest years the availability of high-resolution DEM's from stereo-photogrammetry (2007) and UAV-photogrammetry (2014 and 2016) has allowed an improved analysis of the glacier ice-mass balance within time. During summer 2016 a methodology to record the local disruption processes has been investigated. The presence of vertical and sub-vertical surfaces has motivated the use of Structure-from-Motion Photogrammetry from ground-based stations, which yielded results comparable to the ones achieved using a long-range terrestrial laser scanner. This technique may be assumed as benchmarking for accuracy assessment, but is more difficult to be operated in high-mountain areas. Nevertheless, the measurement of GCP's for the terrestrial photogrammetric project has revealed to be a complex task, involving the need of a total station a GNSS. The effect of network geometry on the final output has also been investigated for SfM-Photogrammetry, considering the severe limitations implied in the Alpine environment. [ABSTRACT FROM AUTHOR]

To date, it has been challenging for clinicians and researchers alike to use the multiple outcome measures available to create a meaningful clinical picture and perform effective longitudinal follow-up. It has been found that instrumented gait analysis can provide information associated with a patient's performance and help to remedy the shortcomings of the currently available outcome measures. The goal of this methodological article is to set the background and justify a new outcome measure inspired by the motor control theories to analyze gait using spatiotemporal parameters. The method is applied in a population of individuals living with Friedreich's ataxia (FRDA), a neurodegenerative disease. The sample population consisted of 19 subjects, 11 to 65 years of age with FRDA, who either ambulated independently, with a cane, or with a rollator. Three scores based on the distance from healthy normative data were used: Organization Score, Variability Score, and an overall measurement, the Global Ambulation Score. The scores were then compared to the Scale for Assessment and Rating of Ataxia (SARA) Gait Score (SARA-GS), a clinical scale currently being used for gait analysis in FRDA. Organization Scores demonstrated a longitudinal deterioration in the gait characteristics from independent ambulators to those who ambulated with a rollator. Variability Scores mostly reflected dynamic instability, which became greater as the requirement of an ambulation aid or the switch from a cane to a rollator was imminent. The global value given by the Global Ambulation Score, which takes into consideration both the Organization Score, the Variability Score, and the level of assistive device, demonstrated a logarithmic relationship with the SARA-GS. Overall, these results highlight that both components introduced should be analyzed concurrently and suggest that the Global Ambulation Score may be a valuable outcome measure for longitudinal disease progression.

Hereditary diseases are caused by mutations in genes, and more than 7,000 rare diseases affect over 30 million Americans. For more than 30 years, hundreds of researchers have maintained that genetic modifications would provide effective treatments for many inherited human diseases, offering durable and possibly curative clinical benefit with a single treatment. This review is limited to gene therapy using adeno-associated virus (AAV) because the gene delivered by this vector does not integrate into the patient genome and has a low immunogenicity. There are now five treatments approved for commercialization and currently available, i.e., Luxturna, Zolgensma, the two chimeric antigen receptor T cell (CAR-T) therapies (Yescarta and Kymriah), and Strimvelis (the gammaretrovirus approved for adenosine deaminase-severe combined immunodeficiency [ADA-SCID] in Europe). Dozens of other treatments are under clinical trials. The review article presents a broad overview of the field of therapy by in vivo gene transfer. We review gene therapy for neuromuscular disorders (spinal muscular atrophy [SMA]; Duchenne muscular dystrophy [DMD]; X-linked myotubular myopathy [XLMTM]; and diseases of the central nervous system, including Alzheimer's disease, Parkinson's disease, Canavan disease, aromatic l-amino acid decarboxylase [AADC] deficiency, and giant axonal neuropathy), ocular disorders (Leber congenital amaurosis, age-related macular degeneration [AMD], choroideremia, achromatopsia, retinitis pigmentosa, and X-linked retinoschisis), the bleeding disorder hemophilia, and lysosomal storage disorders., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Friedreich ataxia (FA) is a progressive genetic neurodegenerative disorder with no approved treatment. Omaveloxolone, an Nrf2 activator, improves mitochondrial function, restores redox balance, and reduces inflammation in models of FA. We investigated the safety and efficacy of omaveloxolone in patients with FA., Methods: We conducted an international, double-blind, randomized, placebo-controlled, parallel-group, registrational phase 2 trial at 11 institutions in the United States, Europe, and Australia (NCT02255435, EudraCT2015-002762-23). Eligible patients, 16 to 40 years of age with genetically confirmed FA and baseline modified Friedreich's Ataxia Rating Scale (mFARS) scores between 20 and 80, were randomized 1:1 to placebo or 150mg per day of omaveloxolone. The primary outcome was change from baseline in the mFARS score in those treated with omaveloxolone compared with those on placebo at 48 weeks., Results: One hundred fifty-five patients were screened, and 103 were randomly assigned to receive omaveloxolone (n = 51) or placebo (n = 52), with 40 omaveloxolone patients and 42 placebo patients analyzed in the full analysis set. Changes from baseline in mFARS scores in omaveloxolone (-1.55 ± 0.69) and placebo (0.85 ± 0.64) patients showed a difference between treatment groups of -2.40 ± 0.96 (p = 0.014). Transient reversible increases in aminotransferase levels were observed with omaveloxolone without increases in total bilirubin or other signs of liver injury. Headache, nausea, and fatigue were also more common among patients receiving omaveloxolone., Interpretation: In the MOXIe trial, omaveloxolone significantly improved neurological function compared to placebo and was generally safe and well tolerated. It represents a potential therapeutic agent in FA. ANN NEUROL 2021;89:212-225., (© 2020 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

The nuclear magnetic resonance (NMR) of alkali-metal ion nuclei (super 7)Li in magnetic molecular rings is discussed. Slow electronic spin dynamics are found at temperatures of the order of J/k(sub B) in the (super 7)Li and (super 1)H NSLR.

The Wnt/ β -catenin signaling is a conserved pathway that has a crucial role in embryonic and adult life. Dysregulation of the Wnt/ β -catenin pathway has been associated with diseases including cancer, and components of the signaling have been proposed as innovative therapeutic targets, mainly for cancer therapy. The attention of the worldwide researchers paid to this issue is increasing, also in view of the therapeutic potential of these agents in diseases, such as Parkinson's disease (PD), for which no cure is existing today. Much evidence indicates that abnormal Wnt/ β -catenin signaling is involved in tumor immunology and the targeting of Wnt/ β -catenin pathway has been also proposed as an attractive strategy to potentiate cancer immunotherapy. During the last decade, several products, including naturally occurring dietary agents as well as a wide variety of products from plant sources, including curcumin, quercetin, berberin, and ginsenosides, have been identified as potent modulators of the Wnt/ β -catenin signaling and have gained interest as promising candidates for the development of chemopreventive or therapeutic drugs for cancer. In this review we make an overview of the nature-derived compounds reported to have antitumor activity by modulating the Wnt/ β -catenin signaling, also focusing on extraction methods, chemical features, and bio-activity assays used for the screening of these compounds., (© 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

A combination of carbon ions/photons irradiation and hyperthermia as a novel therapeutic approach for the in-vitro treatment of pancreatic cancer BxPC3 cells is presented. The radiation doses used are 0-2 Gy for carbon ions and 0-7 Gy for 6 MV photons. Hyperthermia is realized via a standard heating bath, assisted by magnetic fluid hyperthermia (MFH) that utilizes magnetic nanoparticles (MNPs) exposed to an alternating magnetic field of amplitude 19.5 mTesla and frequency 109.8 kHz. Starting from 37 °C, the temperature is gradually increased and the sample is kept at 42 °C for 30 min. For MFH, MNPs with a mean diameter of 19 nm and specific absorption rate of 110 ± 30 W/g Fe3 o 4 coated with a biocompatible ligand to ensure stability in physiological media are used. Irradiation diminishes the clonogenic survival at an extent that depends on the radiation type, and its decrease is amplified both by the MNPs cellular uptake and the hyperthermia protocol. Significant increases in DNA double-strand breaks at 6 h are observed in samples exposed to MNP uptake, treated with 0.75 Gy carbon-ion irradiation and hyperthermia. The proposed experimental protocol, based on the combination of hadron irradiation and hyperthermia, represents a first step towards an innovative clinical option for pancreatic cancer.

Recently, adeno-associated virus (AAV)-mediated gene therapies have attracted clinical interest for treating neurodegenerative diseases including spinal muscular atrophy (SMA), Canavan disease (CD), Parkinson's disease (PD), and Friedreich's ataxia (FA). The influx of clinical findings led to the first approved gene therapy for neurodegenerative disorders in 2019 and highlighted new safety concerns for patients. Large doses of systemically administered AAV stimulate host immune responses, resulting in anti-capsid and anti-transgene immunity with implications for transgene expression, treatment longevity, and patient safety. Delivering lower doses directly to the central nervous system (CNS) is a promising alternative, resulting in higher transgene expression with decreased immune responses. However, neuroinflammatory responses after CNS-targeted delivery of AAV are a critical concern. Reported signs of AAV-associated neuroinflammation in preclinical studies include dorsal root ganglion (DRG) and spinal cord pathology with mononuclear cell infiltration. In this review, we discuss ways to manage neuroinflammation, including choice of AAV capsid serotypes, CNS-targeting routes of delivery, genetic modifications to the vector and/or transgene, and adding immunosuppressive strategies to clinical protocols. As additional gene therapies for neurodegenerative diseases enter clinics, tracking biomarkers of neuroinflammation will be important for understanding the impact immune reactions can have on treatment safety and efficacy.

Friedreich's ataxia (FA) is an inherited disease that causes degeneration of the nervous system. Features of FA include proprioceptive and cerebellar deficits leading to impaired muscle coordination and, consequently, dysmetria in force and time of movement. The aim of this study is to characterize dysmetria and its association to disease severity. Also, we examine the neural mechanisms of dysmetria by quantifying the EMG burst area, duration, and time-to-peak of the agonist muscle. Twenty-seven individuals with FA and 13 healthy controls (HCs) performed the modified Functional Ataxia Rating Scale and goal-directed movements with the ankle. Dysmetria was quantified as position and time error during dorsiflexion. FA individuals exhibited greater time but not position error than HCs. Moreover, time error correlated with disease severity and was related to increased agonist EMG burst. Temporal dysmetria is associated to disease severity, likely due to altered activation of the agonist muscle. NEW & NOTEWORTHY For the first time, we quantified spatial and temporal dysmetria and its relation to disease severity in Friedreich's ataxia (FA). We found that FA individuals exhibit temporal but not spatial dysmetria relative to healthy controls. Temporal dysmetria correlated to disease severity in FA and was predicted from an altered activation of the agonist muscle. Therefore, these results provide novel evidence that FA exhibit temporal but not spatial dysmetria, which is different from previous findings on SCA6.

Background: Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), affecting approximately one third of the world's population. Development of an adequate immune response will determine disease progression or progress to chronic infection. Risk of developing TB among human immunodeficiency virus (HIV)-coinfected patients (HIV-TB) is 20-30 times higher than those without HIV infection, and a synergistic interplay between these two pathogens accelerates the decline in immunological functions. TB treatment in HIV-TB coinfected persons is challenging and it has a prolonged duration, mainly due to the immune system failure to provide an adequate support for the therapy. Therefore, we aimed to study the role of the hormone 7-oxo-dehydroepiandrosterone (7-OD) as a modulator of anti-tuberculosis immune responses in the context of HIV-TB coinfection., Methods: A cross-sectional study was conducted among HIV-TB patients and healthy donors (HD). We characterized the ex vivo phenotype of CD4 + T cells and also evaluated in vitro antigen-specific responses by Mtb stimulation of peripheral blood mononuclear cells (PBMCs) in the presence or absence of 7-OD. We assessed lymphoproliferative activity, cytokine production and master transcription factor profiles., Results: Our results show that HIV-TB patients were not able to generate successful anti-tubercular responses in vitro compared to HD, as reduced IFN-γ/IL-10 and IFN-γ/IL-17A ratios were observed. Interestingly, treatment with 7-OD enhanced Th1 responses by increasing Mtb-induced proliferation and the production of IFN-γ and TNF-α over IL-10 levels. Additionally, in vitro Mtb stimulation augmented the frequency of cells with a regulatory phenotype, while 7-OD reduced the proportion of these subsets and induced an increase in CD4 + T-bet+ (Th1) subpopulation, which is associated with clinical data linked to an improved disease outcome., Conclusions: We conclude that 7-OD modifies the cytokine balance and the phenotype of CD4 + T cells towards a more favorable profile for mycobacteria control. These results provide new data to delineate novel treatment approaches as co-adjuvant for the treatment of TB.

Introduction: Effect-based methods (EBMs), i.e. in vitro and in vivo bioassays, represent innovative tools for the effect detection of environmental chemical pollutants on living organisms. The aim of this study was to evaluate the water quality of a river ecosystem implementing two in vivo bioassays on target freshwater animal species: the crustacean Daphnia magna and the small fish Danio rerio, also known as zebrafish., Materials and Methods: The methods applied in this study, i.e. the Daphnia sp. Acute Immobilisation assay and the Fish Embryo Acute Toxicity (FET) test, are commonly used in water quality research and their application in short-term ecotoxicity detection is suggested by recent European projects. Two sampling sites were chosen in the urban part of the Tiber River in Rome, while a third one was chosen as a reference site in the Farfa River, a tributary upstream of the city. The sites in the Tiber River are potentially affected by different pollution sources, including urban and industrial wastewater discharges, the pesticide release, livestock waste products, and waste dumps., Results and Discussion: The results of the study showed wide differences between the two applied bioassays. The FET test was generally more sensitive in detecting even low effects in all the water samples, but the strongest statistically results were observed with the D. magna Acute Immobilisation test. The results of this research confirm the effectiveness of EBMs in investigating and monitoring water chemical pollution, and stress the need for performing further studies, e.g. chemical analyses and other bioassays, to improve the knowledge of the health status of the Tiber River basin., Conclusions: Further results will aim to support the local authorities in adopting measures to reduce and to eliminate the sources of chemical pollution in the study area.

Sexual differences are commonly described as male-biased sexual dimorphism, female-biased dimorphism, and monomorphism. Nevertheless, detailed patterns of sexual dimorphism have only been explored in a few rodent species. We used geometric morphometrics to investigate patterns of sexual dimorphism, static allometry, and modularity in the skull of the Ethiopian white-footed mouse ( Stenocephalemys albipes ). Procrustes analysis of variance showed nonsignificant sexual dimorphism for the size and shape of the cranium. Significant sexual differences were detected in the mandibular size but not in the mandibular shape. Discriminant analysis indicated nonsignificant differences between sexes in the Procrustes distance of the cranium and mandible. Additionally, scatter allometric plots demonstrated similar patterns of allometry in both sexes. Allometric variation showed an elongation of the rostrum, widening of the zygomatic bones, and narrowing of the braincase. We also observed an expanding of the ascending ramus and shortening of the alveolar part for the mandible. These may indicate the existence of modularity in the skull, which was supported by modularity analysis. Although these trends have been thought to be a growth-related phenomenon of the mammalian skull, functional requirements may also have an effect. In conclusion, our results indicate sexual monomorphism in the skull of S. albipes , which may have no effect on allometric variation and modularity patterns.

Pompe disease is a neuromuscular disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), hydrolyzing glycogen to glucose. Pathological glycogen storage, the hallmark of the disease, disrupts the metabolism and function of various cell types, especially muscle cells, leading to cardiac, motor, and respiratory dysfunctions. The spectrum of Pompe disease manifestations spans two main forms: classical infantile-onset (IOPD) and late-onset (LOPD). IOPD, caused by almost complete GAA deficiency, presents at birth and leads to premature death by the age of 2 years without treatment. LOPD, less severe due to partial GAA activity, appears in childhood, adolescence, or adulthood with muscle weakness and respiratory problems. Since 2006, enzyme replacement therapy (ERT) has been approved for Pompe disease, offering clinical benefits but not a cure. However, advances in early diagnosis through newborn screening, recognizing disease manifestations, and developing improved treatments are set to enhance Pompe disease care. This article reviews recent progress in ERT and ongoing translational research, including the approval of second-generation ERTs, a clinical trial of in utero ERT, and preclinical development of gene and substrate reduction therapies. Notably, gene therapy using intravenous delivery of adeno-associated virus (AAV) vectors is in phase I/II clinical trials for both LOPD and IOPD. Promising data from LOPD trials indicate that most participants met the criteria to discontinue ERT several months after gene therapy. The advantages and challenges of this approach are discussed. Overall, significant progress is being made towards curative therapies for Pompe disease. While several challenges remain, emerging data are promising and suggest the potential for a once-in-a-lifetime treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The aim of the study was to assess the impact of the Saccharomyces boulardii RC009 alone and in combination with a phytase on productive performance, biochemistry, apparent ileal phosphorus digestibility, genotoxicity and histomorphometric parameters in replacement of growth-promoting antibiotics. Two hundred and four 1-day-old male broiler chickens were weighed and redistributed in 3 replicates per treatment with 17 broilers chickens each. Throughout the 49-day experimental period, the broiler chickens were provided with both starter and finisher diets corresponding to each treatment. Treatments (T) were T1: basal diet (BD - control with AGP); T2: BD (without AGP) + S. boulardii RC009 (200g/T, 1 x 1012 CFU/T feed); T3: BD (without AGP) + S. boulardii RC009) + phytase (1000 FTU/T); T4: BD (without AGP) + phytase. The results showed that all treatments were able to improve the productive parameters studied such as DWG and DFI (P=0.05) when compared to the control. The T3 had the highest value followed by T4 and T2. The best value of CI was obtained for T2 followed by T3 and T4. There is no effect of the probiotic or the enzyme alone or in combination on the biochemical parameters evaluated. The treatment T3 improved the weight of leg-thigh and poultry breast (P=0.05). The digestibility of phosphorus showed significant differences between treatments (P=0.05). The histomorphometric parameters were significantly influenced, impacting both the radio and absorptive surface areas, T3 had the best absorptive surface area. The frequency of micronucleus in bone marrow cells of broiler chickens was not affected by any of the studied treatments. The utilization of S. boulardii RC009 alone or combined with phytase notably enhanced productivity parameters, economically significant carcass weight, and histomorphometric characteristics in the small intestine. Moreover, they did not exert toxicity. These results suggest their promising potential for use either independently or in combination as substitutes for antibiotic growth promoters. [ABSTRACT FROM AUTHOR]