Organic Donor-Acceptor-Donor Trimers Nanoparticles Stabilized by Amphiphilic Block Copolymers for Photocatalytic Generation of H2.

Photocatalytic generation of H2 via water splitting emerges as a promising avenue for the next generation of green hydrogen due to its low carbon footprint. Herein, a versatile platform is designed to the preparation of functional π-conjugated organic nanoparticles dispersed in aqueous phase via mini-emulsification. Such particles are composed of donor-acceptor-donor (DAD) trimers prepared via Stille coupling, stabilized by amphiphilic block copolymers synthesized by reversible addition-fragmentation chain transfer polymerization. The hydrophilic segment of the block copolymers will not only provide colloidal stability, but also allow for precise control over the surface functionalization. Photocatalytic tests of the resulting particles for H2 production resulted in promising photocatalytic activity (≈0.6 mmol g-1 h-1). This activity is much enhanced compared to that of DAD trimers dispersed in the water phase without stabilization by the block copolymers.

Solid-State NMR Characterization of Mefloquine Resinate Complexes Designed for Taste-Masking Pediatric Formulations.

Mefloquine (MQ) is an antimalarial medication prescribed to treat or malaria prevention.. When taken by children, vomiting usually occurs, and new doses of medication frequently need to be taken. So, developing pediatric medicines using taste-masked antimalarial drug complexes is mandatory for the success of mefloquine administration. The hypothesis that binding mefloquine to an ion-exchange resin (R) could circumvent the drug's bitter taste problem was proposed, and solid-state 13C cross-polarization magic angle spinning (CPMAS) NMR was able to follow MQ-R mixtures through chemical shift and relaxation measurements. The nature of MQ-R complex formation could then be determined. Impedimetric electronic tongue equipment also verified the resinate taste-masking efficiency in vitro. Variations in chemical shifts and structure dynamics measured by proton relaxation properties (e.g., T1ρH) were used as probes to follow the extension of mixing and specific interactions that would be present in MQ-R. A significant decrease in T1ρH values was observed for MQ carbons in MQ-R complexes, compared to the ones in MQ (from 100-200 ms in MQ to 20-50 ms in an MQ-R complex). The results evidenced that the cationic resin interacts strongly with mefloquine molecules in the formulation of a 1:1 ratio complex. Thus, 13C CPMAS NMR allowed the confirmation of the presence of a binding between mefloquine and polacrilin in the MQ-R formulation studied.

New Perspectives of Deep Brain Stimulation Indications for Parkinson's Disease: A Critical Review.

Deep Brain Stimulation (DBS) is an effective treatment option for patients with dopaminergic complications of Parkinson's disease (PD) and drug-refractory PD tremor. However, DBS and its indications can be challenging, and they are not often debated in the medical community. Through a critical narrative review, the objective of this paper is to improve the comprehension of DBS indications and help to solve the puzzle that this process can be. Proper patient selection is the first step for a good surgical outcome. In this review, then, relevant considerations are discussed, involving PD genes, PD phenotypes, indications of early stages, non-motor symptoms, neuroimaging predictors, comorbidities, and age. Individualized approaches are encouraged, including clinical and radiological factors. Social support during the whole follow-up and expectations alignment are necessary through this process and are also debated.

Myoclonus improvement after seizures in progressive myoclonic epilepsy type 7: a case report.

BACKGROUND: Progressive Myoclonic Epilepsy (PME) is a group of rare diseases that are difficult to differentiate from one another based on phenotypical characteristics. CASE REPORT: We report a case of PME type 7 due to a pathogenic variant in KCNC1 with myoclonus improvement after epileptic seizures. DISCUSSION: Myoclonus improvement after seizures may be a clue to the diagnosis of Progressive Myoclonic Epilepsy type 7.

X-Linked Levodopa-Responsive Parkinsonism-Epilepsy Syndrome: A Novel PGK1 Mutation and Literature Review.

BACKGROUND: Genetic underpinnings in Parkinson's disease (PD) and parkinsonian syndromes are challenging, and recent discoveries regarding their genetic pathways have led to potential gene-specific treatment trials. CASES: We report 3 X-linked levodopa (l-dopa)-responsive parkinsonism-epilepsy syndrome cases due to a hemizygous variant in the phosphoglycerate kinase 1 (PGK1) gene. The likely pathogenic variant NM_000291.4 (PGK1):c.950G > A;p.(Gly317Asp) was identified in a hemizygous state. LITERATURE REVIEW: Only 8 previous cases have linked this phenotype to PGK1, a gene more commonly associated with hemolytic anemia and myopathy. The unusual association of epilepsy, psychiatric symptoms, action tremor, limb dystonia, cognitive symptoms, and l-dopa-responsive parkinsonism must draw attention to PGK1 mutations, especially because this gene is absent from most commercial hereditary parkinsonism panels. CONCLUSIONS: This report aims to shed light on an overlooked gene that causes hereditary parkinsonian syndromes. Further research regarding genetic pathways in PD may provide a better understanding of its pathophysiology and open possibilities for new disease-modifying trials, such as SNCA, LRRK2, PRKN, PINK1, and DJ-1 genes.

Streamlining the Generation of Advanced Polymer Materials Through the Marriage of Automation and Multiblock Copolymer Synthesis in Emulsion.

Synthetic polymers are of paramount importance in modern life - an incredibly wide range of polymeric materials possessing an impressive variety of properties have been developed to date. The recent emergence of artificial intelligence and automation presents a great opportunity to significantly speed up discovery and development of the next generation of advanced polymeric materials. We have focused on the high-throughput automated synthesis of multiblock copolymers that comprise three or more distinct polymer segments of different monomer composition bonded in linear sequence. The present work has exploited automation to prepare high molar mass multiblock copolymers (typically>100,000 g mol-1) using reversible addition-fragmentation chain transfer (RAFT) polymerization in aqueous emulsion. A variety of original multiblock copolymers have been synthesised via a Chemspeed robot, exemplified by a multiblock copolymer comprising thirteen constituent blocks. Moreover, libraries of copolymers of randomized monomer compositions (acrylates, acrylamides, methacrylates, and styrenes), block orders, and block lengths were also generated, thereby demonstrating the robustness of our synthetic approach. One multiblock copolymer contained all four monomer families listed in the pool, which is unprecedented in the literature. The present work demonstrates that automation has the power to render complex and laborious syntheses of such unprecedented materials not just possible, but facile and straightforward, thus representing the way forward to the next generation of complex macromolecular architectures.

Morphological assessment of the isthmus in mesial root canals of first mandibular molars / Avaliação morfológica do istmo nos canais radiculares mesiais dos primeiros molares inferiores

ABSTRACT Root canal morphology and its anatomical variations pose a great challenge to endodontists Aim The aim of this in silico study was to perform a qualitative and quantitative analysis of the threedimensional morphological characteristics of the isthmus in the mesial root canals of mandibular molars using microcomputed tomography (micro-CT) Material and Method Six hundred first mandibular molars were selected, including 317 with two mesial canals with isthmuses between the canals, and fully formed root. Isthmus morphology was determined in 3D longitudinal sections using Fan et al. (2010) classification. Root length, and the volume and area of apical and coronal level were measured. Additionally, the structural model index (SMI) of the canals were also assessed Results The prevalence of isthmuses in the mesial root canals was 32% type II, 29% type III, 22% type IV, and 17% type I. The root length was found to be 9.1±0.5 mm, the volume and area, of all root canal system, were 41.8±40.1 mm3 and 63.6±24.2 mm2 respectively. The isthmi volume and area alone were 11.06±9.03 mm3 and 30.02±11.02 mm2. The study confirmed that isthmuses are present in mesial canals of mandibular first molars, being more frequent in the apical third Conclusion The high prevalence of isthmuses with complex morphological features underscores the importance of using intracanal medications to disinfect areas unprepared by instruments.

RESUMO A morfologia do canal radicular e suas variações anatômicas representam um grande desafio para os endodontistas. O objetivo deste estudo ex vivo foi realizar uma análise qualitativa e quantitativa das características morfológicas tridimensionais do istmo nos canais mesiais de molares inferiores por meio de microtomografia computadorizada (micro-CT) Material e Método Foram selecionados 600 primeiros molares inferiores, incluindo 317 com dois canais mesiais com istmos e raiz totalmente formada. A morfologia do istmo foi determinada em cortes longitudinais 3D usando a classificação Fan et al. (2010). Foram mensurados o comprimento da raiz, o volume e a área apical e coronal e da cavidade pulpar. Adicionalmente, também foram avaliados o structure model index (SMI) dos canais Resultados A prevalência de istmos nos canais mesiais foi de 32% tipo II, 29% tipo III, 22% tipo IV e 17% tipo I. O comprimento da raiz foi de 9,1±0,5 mm, o volume e a área de todo o sistema de canais radiculares foram de 41.8±40.1 mm3 e 63.6±24.2 mm2, respectivamente. O volume e área do istmo isoladamente foram 11.06±9,03 mm3 e 30.02±11.02 mm2. O estudo confirmou que os istmos estão presentes em canais mesiais dos primeiros molares inferiores, sendo mais frequentes no terço apical Conclusão A alta prevalência de istmos com características morfológicas complexas ressalta a importância do uso de medicação intracanal para desinfecção de áreas não tocadas por instrumentos.

Molecular Photoswitching of Main-Chain α-Bisimines in Solid-State Polymers.

Photoisomerization of chromophores usually shows significantly less efficiency in solid polymers than in solution as strong intermolecular interactions lock their conformation. Herein, we establish the impact of macromolecular architecture on the isomerization efficiency of main-chain-incorporated chromophores (i.e., α-bisimine) in both solution and the solid state. We demonstrate that branched architectures deliver the highest isomerization efficiency for the main-chain chromophore in the solid state─remarkably as high as 70% compared to solution. The macromolecular design principles established herein for efficient solid-state photoisomerization can serve as a blueprint for enhancing the solid-state isomerization efficiency for other polymer systems, such as those based on azobenzenes.

Multiblock copolymer synthesis via RAFT emulsion polymerization.

A multiblock copolymer is a polymer of a specific structure that consists of multiple covalently linked segments, each comprising a different monomer type. The control of the monomer sequence has often been described as the "holy grail" of synthetic polymer chemistry, with the ultimate goal being synthetic access to polymers of a "perfect" structure, where each monomeric building block is placed at a desired position along the polymer chain. Given that polymer properties are intimately linked to the microstructure and monomer distribution along the constituent chains, it goes without saying that there exist seemingly endless opportunities in terms of fine-tuning the properties of such materials by careful consideration of the length of each block, the number and order of blocks, and the inclusion of monomers with specific functional groups. The area of multiblock copolymer synthesis remains relatively unexplored, in particular with regard to structure-property relationships, and there are currently significant opportunities for the design and synthesis of advanced materials. The present review focuses on the synthesis of multiblock copolymers via reversible addition-fragmentation chain transfer (RAFT) polymerization implemented as aqueous emulsion polymerization. RAFT emulsion polymerization offers intriguing opportunities not only for the advanced synthesis of multiblock copolymers, but also provides access to polymeric nanoparticles of specific morphologies. Precise multiblock copolymer synthesis coupled with self-assembly offers material morphology control on length scales ranging from a few nanometers to a micrometer. It is imperative that polymer chemists interact with physicists and material scientists to maximize the impact of these materials of the future.

Recent Advances in the Treatment of Genetic Forms of Parkinson's Disease: Hype or Hope?

Parkinson's disease (PD) is a multifarious neurodegenerative disease. Its pathology is characterized by a prominent early death of dopaminergic neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies with aggregated α-synuclein. Although the α-synuclein pathological aggregation and propagation, induced by several factors, is considered one of the most relevant hypotheses, PD pathogenesis is still a matter of debate. Indeed, environmental factors and genetic predisposition play an important role in PD. Mutations associated with a high risk for PD, usually called monogenic PD, underlie 5% to 10% of all PD cases. However, this percentage tends to increase over time because of the continuous identification of new genes associated with PD. The identification of genetic variants that can cause or increase the risk of PD has also given researchers the possibility to explore new personalized therapies. In this narrative review, we discuss the recent advances in the treatment of genetic forms of PD, focusing on different pathophysiologic aspects and ongoing clinical trials.

Recurrent giant neobladder calculus extrusion after bladder exstrophy repair.

Introduction: Patients with bladder exstrophy subjected to reconstructive surgeries are at risk of developing urinary calculus. Case presentation: We report the case of a 29-year-old male patient with bladder exstrophy who presented with a recurrent episode of extrusion of calculus through the neobladder and anterior abdominal wall. Calculus removal and reconstructive repair of the neobladder and abdominal wall were performed in 2010. Nine years following the procedure, the patient returned with new large neobladder calculus extrusion. Conclusion: Recurrence of large calculus should be seen as the new paradigm for the importance of close follow-up in bladder exstrophy patients.

Electrochemically-Initiated RAFT Synthesis of Low Dispersity Multiblock Copolymers by Seeded Emulsion Polymerization.

We describe electrochemically initiated emulsion polymerization with reversible addition-fragmentation chain transfer (eRAFT) to form well-defined multiblock copolymers with low molar mass dispersity. We demonstrate the utility of our emulsion eRAFT process with the synthesis of low dispersity multiblock copolymers by seeded RAFT emulsion polymerization at ambient temperature (∼30 °C). Thus, a triblock, poly(butyl methacrylate)-block-polystyrene-block-poly(4-methylstyrene) [PBMA-b-PSt-b-PMS], and a tetrablock, poly(butyl methacrylate)-block-polystyrene-block-poly(styrene-stat-butyl acrylate)-block-polystyrene [PBMA-b-PSt-b-P(BA-stat-St)-b-PSt], were synthesized as free-flowing, colloidally stable latexes commencing with a surfactant-free poly(butyl methacrylate) macroRAFT agent seed latex. A straightforward sequential addition strategy with no intermediate purification steps was able to be employed due to the high monomer conversions achieved in each step. The method takes full advantage of compartmentalization phenomena and the nanoreactor concept described in previous work to achieve the predicted molar mass, low molar mass dispersity (D ∼ 1.1-1.2), incrementing particle size (Zav = 100-115 nm), and low particle size dispersity (PDI ∼ 0.02) for each generation of the multiblocks.

An Extremely Rare and Demanding Diagnosis of Primary Renal Synovial Sarcoma: A Case Report.

Primary renal synovial sarcoma (PRSS) is an extremely rare malignancy. The diagnosis of PRSS is unforeseen due to the absence of clinical and radiological typical aspects. Here, we present a case of a 69-year-old male with complaints of hematuria and left lumbar pain. Abdominal-pelvic computed tomography scan with contrast injection showed a solid mass of 8cm diameter in the left kidney and renal vein tumor thrombus. The patient was further subjected to robotic-assisted left radical nephrectomy and renal vein thrombectomy. We concomitantly performed left adrenalectomy and paraaortic lymphadenectomy. Immunohistochemical and genetic analysis revealed PRSS. This entity is characterized by abnormal chromosomal translocation t(X;18)(p11.2; q11.2) and consequently the characteristic SYT-SSX fusion gene. Due to the disease's rarity and severity, diagnosis and management of PRSS rely upon a demanding and multidisciplinary approach.

Morphological assessment of the isthmus in mesial root canals of first mandibular molars.

Root canal morphology and its anatomical variations pose a great challenge to endodontists. Aim: The aim of this in silico study was to perform a qualitative and quantitative analysis of the threedimensional morphological characteristics of the isthmus in the mesial root canals of mandibular molars using microcomputed tomography (micro-CT). Material and Method: Six hundred first mandibular molars were selected, including 317 with two mesial canals with isthmuses between the canals, and fully formed root. Isthmus morphology was determined in 3D longitudinal sections using Fan et al. (2010) classification. Root length, and the volume and area of apical and coronal level were measured. Additionally, the structural model index (SMI) of the canals were also assessed. Results: The prevalence of isthmuses in the mesial root canals was 32% type II, 29% type III, 22% type IV, and 17% type I. The root length was found to be 9.1±0.5 mm, the volume and area, of all root canal system, were 41.8±40.1 mm3 and 63.6±24.2 mm2 respectively. The isthmi volume and area alone were 11.06±9.03 mm3 and 30.02±11.02 mm2. The study confirmed that isthmuses are present in mesial canals of mandibular first molars, being more frequent in the apical third. Conclusion: The high prevalence of isthmuses with complex morphological features underscores the importance of using intracanal medications to disinfect areas unprepared by instruments.

A morfologia do canal radicular e suas variações anatômicas representam um grande desafio para os endodontistas. O objetivo deste estudo ex vivo foi realizar uma análise qualitativa e quantitativa das características morfológicas tridimensionais do istmo nos canais mesiais de molares inferiores por meio de microtomografia computadorizada (micro-CT). Material e Método: Foram selecionados 600 primeiros molares inferiores, incluindo 317 com dois canais mesiais com istmos e raiz totalmente formada. A morfologia do istmo foi determinada em cortes longitudinais 3D usando a classificação Fan et al. (2010). Foram mensurados o comprimento da raiz, o volume e a área apical e coronal e da cavidade pulpar. Adicionalmente, também foram avaliados o structure model index (SMI) dos canais. Resultados: A prevalência de istmos nos canais mesiais foi de 32% tipo II, 29% tipo III, 22% tipo IV e 17% tipo I. O comprimento da raiz foi de 9,1±0,5 mm, o volume e a área de todo o sistema de canais radiculares foram de 41.8±40.1 mm3 e 63.6±24.2 mm2, respectivamente. O volume e área do istmo isoladamente foram 11.06±9,03 mm3 e 30.02±11.02 mm2. O estudo confirmou que os istmos estão presentes em canais mesiais dos primeiros molares inferiores, sendo mais frequentes no terço apical. Conclusão: A alta prevalência de istmos com características morfológicas complexas ressalta a importância do uso de medicação intracanal para desinfecção de áreas não tocadas por instrumentos.

An Unexpected and Unpredictable Emergence of Muscle-Invasive Bladder Cancer in a Patient Successfully Treated With Nivolumab for Small-Cell Bladder Cancer.

Small-cell bladder cancer (SCBC) is a rare subtype of bladder cancer with aggressive behavior and poor prognosis. Here, we report the case of a 50-year-old man who presented with hematuria for one month. A computed tomography scan showed an exophytic lesion on the right posterolateral wall of the bladder and a single liver metastasis with a 14 mm diameter. Transurethral resection of the bladder tumor was performed, and postoperative examination of the specimen showed muscle-invasive SCBC. Initially, the patient was treated with neoadjuvant chemotherapy. Rapid clinical and imaging deterioration was observed after the premature end of cisplatin and etoposide therapy. Second-line therapy with nivolumab demonstrated systemic and local complete response. However, the patient was further diagnosed with unpredictable and unexpected urothelial muscle-invasive bladder cancer. After 76 months of regular follow-up, imaging workup did not demonstrate SCBC recurrence or urothelial bladder cancer progression. This report highlights this disease's rarity and severity and no typical or even pathognomonic clinical and radiological presentation. Therefore, histopathology and immunohistochemistry findings play a key role in diagnosis. Immunotherapy has opened a new window in cancer treatment and maybe SCBC patients can benefit from it.

Magnetic resonance imaging target fusion biopsy vs. transrectal ultrasound-guided biopsy - A comparative study of ISUP score upgrading risk in the final radical prostatectomy specimen.

OBJECTIVES: The aim of this study was to com-pare the risk of International Society of Urological Pathology (ISUP) score upgrading between magnetic resonance imaging targeted fusion biopsy (MRI-TB) and tran-srectal ultrasound-guided biopsy (TRUS-B) in the final radical prostatectomy (RP) specimen pathological report. MATERIALS AND METHODS: This retrospective single center study included 51 patients with prostate cancer (PCa) diagnosed with MRI-TB and 83 patients diagnosed with TRUS-B between October/2019 and July/2021. We compared the rates of ISUP score upgrading between both groups after robotic-assisted radi-cal prostatectomy (RARP) and the specific transition of each ISUP score based on biopsy modality. The rate of ISUP score concordance and downgrading were also assessed. To define the intra and interobserver concordance for each ISUP score in biopsy and RP specimen for each biopsy modality, the Cohen's Kappa coefficient was calculated. ISUP scores and biopsy modal-ity were selected for multivariate analysis and a logistic regres-sion model was built to provide independent risk factors of ISUP score upgrading. RESULTS: The difference of the rate of upgrading between MRI-TB group and TRUS-B group was statistically significant (p = 0.007) with 42.2% of patients of TRUS-B group experiencing an upgrade in their ISUP score while only 19.6% in MRI-TB group. Concordance and downgrading rates did not statistically differ between the two groups. Strength of concordance using Cohen's Kappa coefficient was fair in both groups but higher in MRI-TB group (TRUS-B group k = 0.230; p < 0.001; concordance: 47%vs. MRI/TB group k = 0.438; p < 0.001; concordance: 62.7%). Biopsy modality and ISUP 1 on biopsy were independent predic-tors of ISUP upgrading after RP. CONCLUSIONS: MRI-TB is highly accurate with lower risk of PCa upgrading after RP than TRUS-B. Patients with ISUP 1 on biopsy have greater susceptibility to upgrading their ISUP score.

Initial experience in the microsurgical treatment of ruptured brain aneurysms in the endovascular era: characteristics and safety of the learning curve in the first 300 consecutively treated patients.

PURPOSE: Currently, there is an increasing tendency to refer only complex aneurysms for microsurgery. The formation of new neurosurgeons dedicated to open vascular neurosurgery becomes challenging in a situation in which complex aneurysms must be dealt with early in the career, raising questions about the safety of the learning curve. METHODS: We analyzed the characteristics and surgical results of the first 300 consecutively treated patients after subarachnoid hemorrhage by a single neurosurgeon. The incidence of surgical complications and clinical outcomes during the learning curve were analyzed, looking for critical periods regarding patient safety. Microsurgical operative times were also studied. RESULTS: A high frequency of wide-necked aneurysms was observed (70.3%), and, as a result, large (> 10 mm), MCA and paraclinoid aneurysms were overrepresented. A statistically significant correlation between surgical experience and clinical outcomes was observed, with progressive surgical experience resulting in a lower incidence of unfavorable outcomes. We also observed a higher frequency of major surgical complications, unfavorable clinical outcomes, and lower complete occlusion rates among the first 40 patients. Microsurgical operative times progressively and significantly decreased during the learning curve. CONCLUSIONS: We observed a high prevalence of wide-necked aneurysms. Young neurosurgeons must be trained and prepared to deal with these aneurysms early in their careers. Although we observed a decrease in unfavorable results with cumulative surgical experience, the first 40 cases were associated with higher rates of major surgical complications, worse clinical outcomes, and lower complete occlusion rates, indicating that this period may be more critical to patient safety.