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Abstract In the forefront of advanced materials, ultra-high molecular weight (UHMW) polymers, renowned for their outstanding mechanical properties, have found extensive applications across various domains. However, their production has encountered a significant challenge: the attainment of UHMW polymers with a low dispersity (Ɖ). Herein, we introduce the pioneering technique of ultrasound (US) initiated polymerization, which has garnered attention for its capability to successfully polymerize a multitude of monomers. This study showcases the synthesis of UHMW polymers with a comparatively low Ɖ ( ≤ 1.1) within a remarkably short duration ( ~ 15 min) through the amalgamation of emulsion polymerization and high-frequency ultrasound-initiated polymerization. Particularly noteworthy is the successful copolymerization of diverse monomers, surpassing the molecular weight and further narrowing the Ɖ compared to their respective homopolymers. Notably, this includes monomers like vinyl acetate, traditionally deemed unsuitable for controlled polymerization. The consistent production and uniform dispersion of radicals during ultrasonication have been identified as key factors facilitating the swift fabrication of UHMW polymers with exceptionally low Ɖ.

An alternative method to efficiently synthesize Core‐Crosslinked Star polymers (arm‐first approach) is described in this work. The star polymers are produced utilizing a two‐step, one‐pot Sono‐RAFT process. N,N′‐dimethylacrylamide (DMA) is used to prepare the arms, whereas N,N′‐methylenebis(acrylamide) (MAA) is employed as the crosslinking agent. The reactions were conducted in an aqueous medium at room temperature. Using the sono‐RAFT approach, polymerization under different applied powers, crosslinker to arm ratios, and degrees of polymerization were investigated to determine the optimal reaction conditions for synthesizing star polymers. By altering the applied power, the reaction time can be decreased by half. Using a triblock arm, a CCS polymer was produced, and the resulting polymer demonstrated a very high arm‐to‐star conversion. [ABSTRACT FROM AUTHOR]

Automation, block copolymers, chain-end fidelity, RAFT polymerization, sequence-control Keywords: automation; block copolymers; chain-end fidelity; RAFT polymerization; sequence-control EN automation block copolymers chain-end fidelity RAFT polymerization sequence-control 1 1 1 09/25/23 20230921 NES 230921 B Automated synthesis of multiblock copolymers b : A robotic polymer synthesis platform conducts polymerization to produce multiblock copolymers with block sequence definition. [Extracted from the article]

Introduction: Neuropathic pain (NP) accounts for 10% of all pain subtypes in multiple sclerosis (MS) patients. There are few tools to support the diagnosis and follow-up of NP. A contact heat evoked potential stimulator (CHEPS) comprises of heat stimulus over the skin to evoke potentials that can be recorded in the scalp. It is a noninvasive method. The function of sensory spinothalamic pathways in MS patients could be assessed using this physiological method. It can be evaluated through questionnaires, such as the Neuropathic Pain Diagnostic Questionnaire (DN4) and the Leeds assessment of neuropathic symptoms and signs (LANSS). The aim of this preliminary study was to evaluate with CHEPS the nociceptive pathways in MS patients presenting NP. Materials and Methods: DN4 and LANSS questionnaires were used as NP screening tools. CHEPS stimuli were applied to the distal legs, distal arms and face, and recorded in Cz and Pz, in accordance with the standard technique. Results: Ten MS patients were analyzed. Two were excluded due to an excess of movement artifact hampering wave analysis. Three patients had absent CHEPS in the face with V neuralgia. One patient had "normal" CHEPS with NP in the legs. Another showed interesting results with absent CHEPS in the leg without NP. In a patient with left radicular pain, CHEPS was not evoked in the left leg only. CHEPS was absent in the legs of one patient with spinal cord relapse. The last patient showed lower amplitude of CHEPS in the left leg with NP. Discussion and Conclusion: CHEPS is a useful and noninvasive tool for NP studies, including MS patients. NP can be provoked by MS lesions in the afferent pathways. It is speculated that in some MS cases it seems that NP results from a central inhibition pathway compromise. In this situation, CHEPS remain normal despite NP. [ABSTRACT FROM AUTHOR]

Introduction: Neurological research includes relatively few studies on nuclear medicine in multiple sclerosis (MS), when compared to MRI. Among the available findings, initial works with single photon emission tomography (SPECT) and positron emission tomography (PET) reveal a reduction in cerebral oxygen consumption and blood flow in patients with MS, while subsequent studies bring more complex results: Rashid et al (2004), for example, showed that hypoperfusion is most evident in the gray matter of primary progressive and secondary progressive MS patients, while increased perfusion in the white matter of relapsing-remitting MS (RRMS) patients may reflect an increase in the number and metabolism of inflammatory and glial cells. In this context, cognitive dysfunction has received increasing attention in MS studies, although most only include structural changes in MRI. It was hypothesized, therefore, that perfusion and functional imaging might have important advantages for understanding the underlying pathophysiological processes. Materials and Methods: A study is proposed using SPECT to evaluate RRMS patients with different degrees of cognitive impairment. Twenty consecutive RRMS patients, adjusted for age, disease duration, Expanded Disability Status Scale and lesion burden on MRI will be submitted to neuropsychological testing, and then SPECT (ECD-99mTC). Results: Expected results include changes in scintigraphic uptake related to cognitive impairment in RRMS patients, as compared to controls. Discussion and Conclusion: We believe that SPECT (ECD-99mTC) will be helpful in the understanding of cognitive impairment processes in RRMS. [ABSTRACT FROM AUTHOR]

The article presents a molecular study of the subspecies status of Epicrates Cenchria complex, or Boinae. It presents a phylogenetic analysis of the species from the genus Epicrates using a portion of the mitochondrial gene cytochrome b. The result taken together with the phylogenetic pattern shows the necessity for a taxonomical revision of the subspecies.

DNA is the major target of radiation therapy of malignant tumors. Ionizing radiation (IR) induces a variety of DNA lesions, including chemically modified bases and strand breaks. The use of proton beam therapy for cancer treatment is ramping up, as it is expected to reduce normal tissue damage. Thus, it is important to understand the molecular mechanisms of recognition, signaling, and repair of DNA damage induced by protons in the perspective of assessing not only the risk associated with human exposure to IR but also the possibility to improve the efficacy of therapy. Here, we used targeted irradiation of nuclear regions of living cells with controlled number of protons at a high spatio-temporal resolution to detect the induced base lesions and characterize the recruitment kinetics of the specific DNA glycosylases to DNA damage sites. We show that localized irradiation with 4 MeV protons induces, in addition to DNA double strand breaks (DSBs), the oxidized bases 7,8-dihydro-8-oxoguanine (8-oxoG) and thymine glycol (TG) at the site of irradiation. Consistently, the DNA glycosylases OGG1 and NTH1, capable of excising 8-oxoG and TG, respectively, and initiating the base excision repair (BER) pathway, are recruited to the site of damage. To our knowledge, this is the first direct evidence indicating that proton microbeams induce oxidative base damage, and thus implicating BER in the repair of DNA lesions induced by protons., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest. There was no financial or non-financial assistance provided by a third party for the reported work. There are no patents or copyrights relevant to this work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

DNA integrity is incessantly confronted to agents inducing DNA lesions. All organisms are equipped with a network of DNA damage response mechanisms that will repair DNA lesions and restore proper cellular activities. Despite DNA repair mechanisms have been revealed in replicating cells, still little is known about how DNA lesions are repaired in postmitotic cells. Muscle fibers are highly specialized postmitotic cells organized in syncytia and they are vulnerable to age-related degeneration and atrophy after radiotherapy treatment. We have studied the DNA repair capacity of muscle fiber nuclei and compared it with the one measured in proliferative myoblasts here. We focused on the DNA repair mechanisms that correct ionizing radiation (IR)-induced lesions, namely the base excision repair, the nonhomologous end joining, and the homologous recombination (HR). We found that in the most differentiated myogenic cells, myotubes, these DNA repair mechanisms present weakened kinetics of recruitment of DNA repair proteins to IR-damaged DNA. For base excision repair and HR, this decline can be linked to reduced steady-state levels of key proteins involved in these processes., (© 2023 Sutcu et al.)

Machines can revolutionize the field of chemistry and material science, driving the development of new chemistries, increasing productivity, and facilitating reaction scale up. The incorporation of automated systems in the field of polymer chemistry has however proven challenging owing to the demanding reaction conditions, rendering the automation setup complex and costly. There is an imminent need for an automation platform which uses fast and simple polymerization protocols, while providing a high level of control on the structure of macromolecules via precision synthesis. This work combines an oxygen tolerant, room temperature polymerization method with a simple liquid handling robot to automatically prepare precise and high order multiblock copolymers with unprecedented livingness even after many chain extensions. The highest number of blocks synthesized in such a system is reported, demonstrating the capabilities of this automated platform for the rapid synthesis and complex polymer structure formation., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Fifty percent of all patients with cancer worldwide require radiotherapy. In the case of brain tumors, despite the improvement in the precision of radiation delivery with proton therapy, studies have shown structural and functional changes in the brains of treated patients with protons. The molecular pathways involved in generating these effects are not completely understood. In this context, we analyzed the impact of proton exposure in the central nervous system area of Caenorhabditis elegans with a focus on mitochondrial function, which is potentially implicated in the occurrence of radiation-induced damage. To achieve this objective, the nematode C. elegans were micro-irradiated with 220 Gy of protons (4 MeV) in the nerve ring (head region) using the proton microbeam, MIRCOM. Our results show that protons induce mitochondrial dysfunction, characterized by an immediate dose-dependent loss of the mitochondrial membrane potential (ΔΨm) associated with oxidative stress 24 h after irradiation, which is itself characterized by the induction of the antioxidant proteins in the targeted region, observed using SOD-1::GFP and SOD-3::GFP strains. Moreover, we demonstrated a two-fold increase in the mtDNA copy number in the targeted region 24 h after irradiation. In addition, using the GFP::LGG-1 strain, an induction of autophagy in the irradiated region was observed 6 h following the irradiation, which is associated with the up-regulation of the gene expression of pink-1 (PTEN-induced kinase) and pdr-1 ( C. elegans parkin homolog). Furthermore, our data showed that micro-irradiation of the nerve ring region did not impact the whole-body oxygen consumption 24 h following the irradiation. These results indicate a global mitochondrial dysfunction in the irradiated region following proton exposure. This provides a better understanding of the molecular pathways involved in radiation-induced side effects and may help in finding new therapies.

In addition to representing a significant part of the natural background radiation exposure, α-particles are thought to be a powerful tool for targeted radiotherapy treatments. Understanding the molecular mechanisms of recognition, signaling, and repair of α-particle-induced DNA damage is not only important in assessing the risk associated with human exposure, but can also potentially help in identifying ways of improving the efficacy of radiation treatment. α-particles (He 2+ ions), as well as other types of ionizing radiation, and can cause a wide variety of DNA lesions, including DNA double-strand breaks (DSBs). In mammalian cells, DNA DSBs can be repaired by two major pathways: non-homologous end-joining (NHEJ) and homologous recombination (HR). Here, we investigated their dynamics in mouse NIH-3T3 cells through the recruitment of key proteins, such as the KU heterodimer for NHEJ and RAD51 for HR upon localized α-particle irradiation. To deliver α-particles, we used the MIRCOM microbeam, which allows targeting of subnuclear structures with submicron accuracy. Using mouse NIH-3T3 cells, we found that the KU heterodimer is recruited much earlier at DNA damage sites marked by H2AX phosphorylation than RAD51. We also observed that the difference in the response of the KU complex and RAD51 is not only in terms of time, but also in function of the chromatin nature. The use of a microbeam such as MIRCOM, represents a powerful tool to study more precisely the cellular response to ionizing irradiation in a spatiotemporal fashion at the molecular level.

Entomopathogenic fungi are naturally occurring microorganisms that attack insect pests, making them exceptional allies when developing biocontrol strategies. A particular aspect of the ecology of these fungi is that they interact not only with insects but also with plants, being able to colonize them endophytically without causing symptoms of disease. The objectives of this study were to determine the endophytic capacity of different species of entomopathogenic fungi in tobacco plants by means of foliar spraying, to evaluate the persistence in planta of the entomopathogens and the effect of endophytes on consumption by coleopteran pests. A total of 24 strains were analyzed to test endophytic capacity at 7, 14, 21 and 28 days post inoculation. A significant effect of the strains was found. On days 7, 14 and 21, the strain that showed the highest colonization percentages was B. bassiana LPSc 1215, and at day 28 B. bassiana strains LPSc 1215 and LPSc 1212 exhibited the best endophytic capacity, maintaining elevated colonization percentages. Choice test results indicated that D. speciosa fed indiscriminately on colonized and non-colonized leaves. The results indicate that B. bassiana LPSc 1215 constitutes a strain that would merit further investigation for the purpose of pest management in tobacco cultivation.

Background: NPHS2 gene variants are associated with focal segmental glomerulosclerosis (FSGS) and steroid-resistant nephrotic syndrome (SRNS). In this study, the prevalence of NPHS2 variants p.R229Q, p.A242V, and p.R138Q was investigated in patients with familial or sporadic FSGS., Materials and Methods: The sample consisted of 40 children and 70 adults diagnosed with FSGS confirmed by renal biopsy. Clinical and laboratory parameters were evaluated. Genotyping for the three single nucleotide polymorphisms (SNPs) was performed by real-time polymerase chain reaction: two variants in exon 5 (p.R229Q and p.A242V) and one in exon 3 (p.R138Q). Variants were correlated with ethnicity, clinical presentation, treatment response, and renal outcomes., Results: Among the 40 children analyzed, 20% had familial and 80% sporadic FSGS and among adults, 4.3% had familial and 95.7% sporadic FSGS, respectively. Overall, SRNS was found in 70% of adults and 90% in children. Among children, variants were detected in 2 (5%) with sporadic FSGS, p.R229Q and p.A242V in 1 each. Among adults, variants were present in 9 (12.9%) patients, all with sporadic FSGS, p.R229Q in 4 and p.A242V in 5. No patient had the p.R138Q variant. Among adults, a trend of higher proteinuria at the end of follow-up (p = 0.06) was found in patients carrying a variant. There was no significant association between NPHS2 variants with the clinical presentation, dependence on immunosuppressive treatment, or renal outcomes. Regarding ethnicity, all patients carrying the p.R229Q variant were White, while 67% of carriers of the p.A242V variant were Black., Conclusion: In these patients with familial or sporadic FSGS, the prevalence of p.R229Q and p.A242V variants in children was 5% and in adults 12.9%. More studies of patients with FSGS could better define a strategy for genetic analysis and therapeutic management.

Charged-particle microbeams (CPMs) provide a unique opportunity to investigate the effects of ionizing radiation on living biological specimens with a precise control of the delivered dose, i.e. the number of particles per cell. We describe a methodology to manipulate and micro-irradiate early stage C. elegans embryos at a specific phase of the cell division and with a controlled dose using a CPM. To validate this approach, we observe the radiation-induced damage, such as reduced cell mobility, incomplete cell division and the appearance of chromatin bridges during embryo development, in different strains expressing GFP-tagged proteins in situ after irradiation. In addition, as the dosimetry of such experiments cannot be extrapolated from random irradiations of cell populations, realistic three-dimensional models of 2 cell-stage embryo were imported into the Geant4 Monte-Carlo simulation toolkit. Using this method, we investigate the energy deposit in various chromatin condensation states during the cell division phases. The experimental approach coupled to Monte-Carlo simulations provides a way to selectively irradiate a single cell in a rapidly dividing multicellular model with a reproducible dose. This method opens the way to dose-effect investigations following targeted irradiation.

Aim: To evaluate the effects of gene polymorphisms in the treatment of erythema nodosum leprosum with prednisone/thalidomide. Patients & methods:  A total of 152 patients from different regions of Brazil were included. Generalized estimating equation was used to evaluate the influence of polymorphisms and haplotypes on the drug dose variation throughout the treatment. Results: An association between the genotype tuberculoid of polymorphism ABCB1 3435C>T (rs1045642; p = 0.02) and prednisone dose was found in the recessive model. An association between the haplotypes 1031T/-863C/-857C/-308A/-238G (p = 0.006) and 1031T/-863C/-857T/-308A/-238G (p = 0.040) of the TNF  gene and the CYP2C19*2 polymorphism were also identified, in relation to thalidomide dosage variation over the course of treatment. Conclusion: This work presents the first pharmacogenetic report of association between gene polymorphisms and erythema nodosum leprosum treatment with prednisone/thalidomide.

Although the thalidomide tragedy occurred more than 50 years ago, the medication is still being used worldwide for different reasons, and several aspects regarding its teratogenicity remain unsolved. Despite the strict regulation implemented, new cases of thalidomide embryopathy (TE) are still being registered in Brazil. Furthermore, the molecular processes that lead to malformations when the embryo is exposed to thalidomide have not yet been fully identified. In this article, we perform a critical analysis of thalidomide's history in Brazil, highlighting aspects of the occurrence of TE over the decades. Finally, we present the main perspectives and challenges for ongoing surveillance and prevention of TE in Brazil. The effective control of dispensing thalidomide, especially in areas where leprosy is endemic, is one of the most important and challenging points. Furthermore, the emergence of thalidomide analogues is fast approaching, and their availability would pose additional concerns. The understanding of the molecular mechanisms and targets of thalidomide in both experimental and human models is essential for generating new insights into teratogenic mechanisms, so that safer thalidomide analogues can be developed., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Some cases of recurrent first trimester miscarriage have a thrombotic etiology. The aim of this study was to investigate the prevalence of the most common thrombophilic mutations - factor V (FV) Leiden G1691A (FVL), prothrombin (FII) G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T - in women with recurrent miscarriages. In this case-control study, we included 137 women with two or more consecutive first-trimester miscarriages (£12 weeks of gestation) and 100 healthy women with no history of pregnancy loss, and with at least one living child. DNA was extracted from the patient samples, and the relevant genes (FVL, FII, and MTHFR) were amplified by PCR, followed by restriction fragment length polymorphism, to assess the polymorphisms in these genes. The allelic frequencies of polymorphisms were not significantly different between the case and control groups. Polymorphisms in the MTHFR, FVL, and FII genes were not associated with recurrent miscarriage during the first trimester of pregnancy in Brazilian women (P = 0.479; P = 0.491 and P = 0.107, respectively). However, the etiologic identification of genetic factors is important for genetic counseling., Competing Interests: The authors declare no conflict of interest.

In 2015 an unprecedented increase of reports of newborns with microcephaly in Brazil made news headlines around the world. A possible etiological association with prenatal maternal infection by Zika virus (ZIKV) was suggested based on temporal and geographic distribution of ZIKV infection and the subsequent increase in the reports of microcephaly cases. Here we discuss ZIKV as a new human teratogen, with comments on potential treatment options., (© 2016 ASCPT.)

Introduction: Thalidomide causes congenital defects in children, such as limb reduction defects. Currently, it is used for a few indications; in Brazil, where leprosy is endemic, thalidomide is used for the treatment of erythema nodosum leprosum, and recent cases of thalidomide embryopathy have been reported., Methods: We analyzed the frequency of births with phenotypes consistent with thalidomide embryopathy (TEP) and correlated this with the distribution of thalidomide and the prevalence of leprosy between 2005 and 2010 in Brazil., Results: A total of 5,889,210 thalidomide tablets were distributed; the prevalence of limb reduction defects was 1.60 (CI95%: 1.54-1.66) and TEP was 0.11 (CI95%: 0.10-0.13) per 10,000 births. Poisson regression showed an increase in cases of TEP and limb reduction defects per 100,000 tablets dispensed. Clusters and geographical isolates were identified in several regions., Conclusions: There is a correlation between thalidomide and TEP showing that thalidomide embryopathy should be monitored in countries where this medication is available., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Different studies demonstrate positive correlations between seminal variables determined in the laboratory and subsequent fertility after artificial insemination. It is clear, however, that there is still a deficiency in predicting in vivo fertility results of semen samples. The present study intended to verify the efficiency of rapid and slow thermoresistance tests in predicting fertility of frozen semen of bulls. Sperm from 64 ejaculates of 39 Nelore bulls (Bos indicus), aged 2-10 years, were cryopreserved in 0.5 mL straws. Thawed straws containing 30 x 10(6) sperm were analyzed for seminal variables in the laboratory and used to inseminate 4920 cows to evaluate fertility in the field. The ejaculates were frozen in a Tris-based extender and samples were evaluated for total motility after rapid (46 degrees C/30 min) and slow (38 degrees C/5h) thermoresistance tests by conventional and computerized (CASA) methods. Sperm samples were grouped according to their ability to retain motility after thermoresistance testing: group 0 (0% motility), group 1 (1-20% total motility), group 2 (21-40% total motility) and group 3 (>40% total motility). Correlation and association between these groups and fertility diagnosed by rectal palpation at 90 days were verified. Chi-square test demonstrated no association between motility groups and fertility (P>0.25) and both rapid and slow thermoresistance tests had a lesser correlation to fertility (r=0.11 and 0.14, respectively). These results demonstrated that these tests are not reliable in predicting in vivo behavior of bull frozen semen and are not effective to estimate fertility.

In this paper the authors study the sites of single lesions in 317 paucibacillary patients registered at the outpatient units of the CMS Jorge Saldanha and the Curupaiti State Hospital in Rio de Janeiro, Brazil. The preferential sites of lesions in the population studied, their relation with age and sex and factors likely to influence their distribution are discussed. The findings are compared with other similar studies performed in Asia and Africa.