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1.
Artigo em Inglês | MEDLINE | ID: mdl-38978456

RESUMO

Eu3+-induced polystyrene-co-poly(acrylic acid) aggregates (EIPAs) were synthesized using a self-assembly approach, and their structures and photophysical characteristics were examined to achieve effective monochromatic red emission in polymer light-emitting diodes (PLEDs). By adjusting the monomer ratio in RAFT polymerization, the size of Eu3+-induced block copolymer nanoaggregates can be regulated, thereby modulating the luminescence intensity. High-performance bilayer polymer light-emitting devices were fabricated using poly(9,9-dioctylfluorene) (PFO) and 2-(tert-butylphenyl)-5-biphenylyl-1,3,4-oxadiazole (PBD) as the host matrix, with EIPAs as the guest dopant. The devices exhibited narrow red emission at 615 nm with a full width at half-maximum (fwhm) of 15 nm across doping concentrations of 1, 3, 5, and 10 wt %. At a doping concentration of 3 wt %, the device achieved a maximum brightness of 1864.48 cd/m2 at 193.82 mA/cm2 and an external quantum efficiency of 3.20% at a current density of 3.5 mA/cm2. These results indicate that incorporating polystyrene-co-poly(acrylic acid) with Eu3+ complexes enhances the excitation and emission intensity, as well as the structural stability of the emitting layer in PLEDs, thereby improving the device performance.

2.
Int J Biol Sci ; 20(8): 2860-2880, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38904024

RESUMO

Mitochondrial diseases are associated with neuronal death and mtDNA depletion. Astrocytes respond to injury or stimuli and damage to the central nervous system. Neurodegeneration can cause astrocytes to activate and acquire toxic functions that induce neuronal death. However, astrocyte activation and its impact on neuronal homeostasis in mitochondrial disease remain to be explored. Using patient cells carrying POLG mutations, we generated iPSCs and then differentiated these into astrocytes. POLG astrocytes exhibited mitochondrial dysfunction including loss of mitochondrial membrane potential, energy failure, loss of complex I and IV, disturbed NAD+/NADH metabolism, and mtDNA depletion. Further, POLG derived astrocytes presented an A1-like reactive phenotype with increased proliferation, invasion, upregulation of pathways involved in response to stimulus, immune system process, cell proliferation and cell killing. Under direct and indirect co-culture with neurons, POLG astrocytes manifested a toxic effect leading to the death of neurons. We demonstrate that mitochondrial dysfunction caused by POLG mutations leads not only to intrinsic defects in energy metabolism affecting both neurons and astrocytes, but also to neurotoxic damage driven by astrocytes. These findings reveal a novel role for dysfunctional astrocytes that contribute to the pathogenesis of POLG diseases.


Assuntos
Astrócitos , DNA Polimerase gama , DNA Polimerase Dirigida por DNA , Mitocôndrias , Mutação , Astrócitos/metabolismo , DNA Polimerase gama/genética , DNA Polimerase gama/metabolismo , Humanos , Mitocôndrias/metabolismo , DNA Polimerase Dirigida por DNA/genética , DNA Polimerase Dirigida por DNA/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Neurônios/metabolismo , Potencial da Membrana Mitocondrial , Células-Tronco Pluripotentes Induzidas/metabolismo , Células Cultivadas , Doenças Mitocondriais/genética , Doenças Mitocondriais/metabolismo , Técnicas de Cocultura
3.
Can J Ophthalmol ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38889882

RESUMO

OBJECTIVE: To study the clinical characteristics and long-term outcomes of patients with noninfectious uveitis (NIU) who are treated with systemic immunomodulatory therapy (IMT). DESIGN: Retrospective case series. PARTICIPANTS: All consecutive cases of adults with NIU under the care of 5 uveitis subspecialty tertiary care clinics between 2010 to 2021 were included. METHODS: Patient outcomes were assessed at initial presentation and at the latest available follow-up. RESULTS: A total of 418 NIU patients receiving IMT therapy with a median age of 46.0 years and 59.3% female were identified. Each patient required an average of 1.4 agents until achieving an optimal response. Following initial treatment with prednisone, patients were most commonly initiated on methotrexate. The top 3 treatments with the highest proportion of optimal treatment response when taken alone or in combination with other agents were infliximab (79.3%), cyclosporine (75%), and adalimumab (70%). The strongest predictors for requiring a greater number of IMTs trialed were younger age, panuveitis, and a chronic or recurrent disease course. Multivariable linear regression analysis suggested that baseline visual acuity at diagnosis was the only significant predictor of final visual acuity (p < 0.001). CONCLUSIONS: NIU patients on IMT are often trialed on multiple therapeutic agents before achieving an optimal treatment response. Visual acuity at diagnosis is a predictor of final visual outcomes, whereas chronic or recurrent disease course, younger age, and panuveitis are predictors of requiring multiagent treatment regimens.

4.
J Neurol ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822839

RESUMO

We aimed to provide a detailed phenotypic description of status epilepticus (SE) in a large cohort of patients with POLG disease and identify prognostic biomarkers to improve the management of this life-threatening condition. In a multinational, retrospective study with data on patients with POLG disease from seven European countries, we identified those who had SE. The age of SE onset, accompanying clinical, laboratory, imaging and genetic findings were analysed. One hundred and ninety-five patients with genetically confirmed POLG disease were recruited, of whom 67% (130/194) had epilepsy. SE was identified in 77% (97/126), with a median age of SE onset of 7 years. SE was the presenting symptom of the disease in 43% (40/93) of those with SE, while 57% (53/93) developed SE during the disease course. Convulsive SE was reported in 97% (91/94) followed by epilepsia partialis continua in 67% (56/84). Liver impairment 78% (74/95), ataxia 69% (60/87), stroke-like episodes 57% (50/88), were the major comorbidities. In the majority (66%; 57/86) with SE this became refractory or super-refractory. The presence of seizures was associated with significantly higher mortality compared to those without (P ≤ 0.001). The median time from SE debut to death was 5 months. SE is a major clinical feature of POLG disease in early and juvenile to adult-onset disease and can be the presenting feature or arise as part of a multisystem disease. It is associated with high morbidity and mortality, with the majority of patients with SE going on to develop refractory or super-refractory SE.

5.
Sci Rep ; 14(1): 10358, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710781

RESUMO

Porosity affects key astromaterial processes from disruption in our atmosphere and impact with the ground, to the comminution of boulders by thermal and impact processes and slope mechanics on asteroid surfaces, to access and utilization of in-situ resources. Whereas the bulk porosity of clay-rich meteorites is well established, the magnitude of their surface area and nano-scale porosity is poorly known. Here we use N2 BET gas adsorption to measure the specific surface area and nanoscale pore distribution in several clay-rich meteorites. Two recent falls Tarda (C2-ung) and Aguas Zarcas (CM2) have specific surface areas of 72.5 and 16.5 m2/g, respectively. However, the specific surface area of Tarda ranges from 33.7 to 81.6 m2/g depending on outgassing conditions. The Tarda surface area is dominated by an interconnected network of ~ 3-nm-sized pores, whereas Aguas Zarcas shows a lower density of ~ 3 nm pores and broader size distribution around 40 nm. In contrast, Ivuna and Orgueil (CI1) have surface areas of ~ 15 to 18 m2/g: the low values compared to Tarda are likely due to the neoformation of pore-blocking minerals during atmospheric exposure. These data suggest that returned samples from asteroids Ryugu and Bennu, which are mineralogically and texturally similar to Tarda, also have interconnected nano-scale porosity with high surface area.

6.
ACS Omega ; 9(18): 19816-19823, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38737078

RESUMO

Candida auris infection has been recognized as an urgent threat to antifungal drug resistance, and the Eagle effect of C. auris FKS1 (1,3-ß-d-glucan synthase) wild-type isolates has also been noted. The Eagle effect, namely, where higher concentrations of antifungals reduce fungicidal activity relative to lower concentrations, is a confounding factor of apparent antifungal resistance, but the detailed mechanism remains unclear. Here, we present the conformational variability of mutation sites for ERG11p (lanosterol 14α-demethylase) and FKS1 from deep neural network-based prediction along with the reported X-ray crystallographic and cryo-electron microscopy (cryo-EM) structures of antifungals. The sequence variability maps provide valuable insights into the inconsistent correlation between azole resistance and the mysterious Eagle effect with the dispersion of minimal inhibitory concentration (MIC) for echinocandin resistance. The conformational variability prediction supports the hypothesis that mutations K143R of clade I, VF125AL of clade III, and Y132F of clade IV for C. auris ERG11p make the corresponding site variable and that an increased population of invisible variable conformations potentially contributes to triazole resistance. In contrast, the predicted rigid conformation by the S639F mutation of hot spot region 1 (HS1) for FKS1 suggests that caspofungin (CAS) is involved in an uncompetitive inhibition, and a decreased population of the CAS-bound state of FKS1 with Rho1 leads to drug resistance. The predicted variable HS1 region for FKS1 WT isolates and the rigid one for FKS1 S639F mutants support the in vivo drug response and the in vitro MIC dispersion. A plausible mechanism of the Eagle effect is hereby proposed, namely, that a high concentration of CAS with a high membrane affinity reduces the population of the CAS-bound state of FKS1 with Rho1, as well as accompanying events such as aggregation or association depending on the conformational variability of HS1.

7.
Transl Androl Urol ; 13(4): 596-612, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38721300

RESUMO

Background: Penile prosthetic devices are the standard treatment for erectile dysfunction (ED) after failure of maximum medical therapy and conservative options. Several penile lengthening procedures (PLPs) can be performed concurrently with penile prosthesis (PP) insertion in patients with severe ED, penile shortening, and/or Peyronie's disease to help combat negative emotional and psychological concerns from penile length loss with penile prosthetic device placement. Methods: An extensive, systematic literature review of the various pre-, intra-, and post-operative techniques that can be applied to preserve, restore or enhance penile length at the time of penile prosthetic implantation. Results: Numerous pre-operative and post-operative inflation protocols exists with vacuum erection devices and penile traction therapy. Intraoperative surgical techniques include cavernosal sparing and channeling without dilatation, subcoronal incision with circumferential penile degloving and grafting, the sliding technique, the modified sliding technique, the multiple-slit technique, the tunical expansion procedure (TEP), modified TEP, and the auxetic expansion procedure. These approaches can be meaningful to restore and/or preserve length for patients undergoing PP insertion. Conclusions: PLPs can be performed by surgeons who have extensive penile reconstruction experience and have been trained to do these procedures, as there is significant risk to the patient and limitations to what can be expected. Each patient must be counseled in detail about the risks and benefits of these procedures and have their expectations managed as the average postoperative penile length recovery is around 3 cm and can range from 0-4.0 cm. Future research is needed to identify the appropriate candidate for each approach, and how much length gain the patient can expect.

8.
Int J Surg Pathol ; : 10668969241234321, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627896

RESUMO

Introduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm2 area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management.

9.
Virchows Arch ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38600174

RESUMO

Based on lineage-specific transcription factors, small-cell neuroendocrine carcinoma (SmCC) of the urinary bladder has recently been subtyped into three molecular subtypes: ASCL1, NEUROD1 and POU2F3. The latter is a master transcriptional regulator of tuft cells (TCs) which are rare solitary cells found in various mucosal epithelia such as the gastrointestinal tract, but which have not been reported in the bladder. The POU2F3 subtype shows low or absent neuroendocrine marker expression. A case of mixed SmCC and conventional-type urothelial carcinoma (CUC) of the urinary bladder with POU2F3-expressing intraepithelial small-cell carcinoma in keeping with a tuft cell phenotype, arising in association with intestinal metaplasia (IM) is described. The presence of POU2F3-expressing cells in normal urothelium, cystitis cystica glandularis and IM of the urinary bladder is demonstrated in separate cases of cystitis cystica glandularis with IM. Also, POU2F3 expression is identified in a subset of bladder SmCC.

10.
Zookeys ; 1196: 121-138, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560096

RESUMO

Historical, nomenclatural, technical, and biological problems associated with the 42 species of Mesothrips are discussed. Type specimens have been re-examined of 14 of the 25 species that were described prior to 1930 and remain known only from imperfectly slide-mounted specimens. As a result, seven new synonyms are recognised. From China, six species of Mesothrips have been listed, but the records of M.alluaudi and M.manii are rejected, and three new species are described: M.jianfengisp. nov., M.longistylussp. nov., and M.verniciasp. nov. These three species are divergent from other members of Mesothrips in lacking a prominent fore tarsal tooth and may indicate a possible generic relationship to the flower-living species in the Asian genus Dolichothrips. An illustrated key is provided to the seven Mesothrips species now known from China.

11.
Ther Adv Urol ; 16: 17562872241241858, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38571490

RESUMO

Background: The increasing popularity of the silicone sleeve penile implant has been accompanied by concerns over potential risks and adverse events. Objectives: To provide multi-institutional data on safety outcomes in patients undergoing silicone sleeve penile implant surgery across high-volume implant surgeons. In addition, we discuss preventative techniques to minimize postoperative complications and the management of these events. Design and methods: We performed a retrospective analysis of men undergoing penile silicone sleeve implants between November 2020 and November 2022 with four surgeons, each from a separate institution. Perioperative and postoperative adverse events, including unsatisfactory cosmetic outcomes requiring revision, were determined by physician follow-up. Flaccid penile length and girth were measured preoperatively and postoperatively. Results: A total of 299 male patients underwent silicone sleeve implant surgery, with an average age of 42.5 ± 10.5 years and an average body mass index of 28.5 ± 4.0. The patient cohort exhibited minimal comorbidities, with 5% having hyperlipidemia, 2% being smokers, 2% having cardiovascular disease, and 1% having diabetes. Patients experienced an average increase of 4.1 ± 1.5 cm in their flaccid penile length (a 50% increase) and an average increase of 3.4 ± 1.5 cm in their flaccid girth (a 37% increase) (p < 0.01). Complication rates included new-onset postoperative erectile dysfunction (0%), infection (1.3%), seroma (2.0%), and erosion (5.0%). The average follow-up time was 11.6 months. Notably, our rates of infection and seroma were lower than those reported in a previous single-center review, while erosion rates were higher. Conclusion: This is the largest study to characterize the safety of the penile silicone sleeve implant across multiple institutions. In men who desire cosmetic size augmentation, silicone sleeve implant surgery is associated with significantly increased flaccid penile length and girth. Complications are mainly cosmetic and may be corrected; however, patients should be appropriately counseled on the risk of erosion, which appears to be higher than previously reported.


Outcomes for penile silicone sleeve surgery This is the largest study to characterize the safety of the penile silicone sleeve implant across multiple institutions. In men who desire cosmetic penile size improvement, the silicone sleeve implant surgery is associated with significantly increased flaccid penile length and girth. Complications are mainly cosmetic and may be corrected, however, patients should be appropriately counseled on the risk of erosion, which appears to be higher than previously reported.

12.
Ticks Tick Borne Dis ; 15(4): 102342, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38613901

RESUMO

Ixodid (hard) ticks play important ecosystem roles and have significant impacts on animal and human health via tick-borne diseases and physiological stress from parasitism. Tick occurrence, abundance, activity, and key life-history traits are highly influenced by host availability, weather, microclimate, and landscape features. As such, changes in the environment can have profound impacts on ticks, their hosts, and the spread of diseases. Researchers recognize that spatial and temporal factors influence activity and abundance and attempt to account for both by conducting replicate sampling bouts spread over the tick questing period. However, common field methods notoriously underestimate abundance, and it is unclear how (or if) tick studies model the confounding effects of factors influencing activity and abundance. This step is critical as unaccounted variance in detection can lead to biased estimates of occurrence and abundance. We performed a descriptive review to evaluate the extent to which studies account for the detection process while modeling tick data. We also categorized the types of analyses that are commonly used to model tick data. We used hierarchical models (HMs) that account for imperfect detection to analyze simulated and empirical tick data, demonstrating that inference is muddled when detection probability is not accounted for in the modeling process. Our review indicates that only 5 of 412 (1 %) papers explicitly accounted for imperfect detection while modeling ticks. By comparing HMs with the most common approaches used for modeling tick data (e.g., ANOVA), we show that population estimates are biased low for simulated and empirical data when using non-HMs, and that confounding occurs due to not explicitly modeling factors that influenced both detection and abundance. Our review and analysis of simulated and empirical data shows that it is important to account for our ability to detect ticks using field methods with imperfect detection. Not doing so leads to biased estimates of occurrence and abundance which could complicate our understanding of parasite-host relationships and the spread of tick-borne diseases. We highlight the resources available for learning HM approaches and applying them to analyzing tick data.


Assuntos
Ixodidae , Animais , Ixodidae/fisiologia , Ixodidae/crescimento & desenvolvimento , Carrapatos/fisiologia , Ecossistema , Modelos Biológicos , Ecologia , Doenças Transmitidas por Carrapatos/epidemiologia
13.
ACS Appl Mater Interfaces ; 16(12): 15121-15132, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38501443

RESUMO

Acquiring the ideal blend morphology of the active layer to optimize charge separation and collection is a constant goal of polymer solar cells (PSCs). In this paper, the ternary strategy and the sequential deposition process were combined to make sufficient use of the solar spectrum, optimize the energy-level structure, regulate the vertical phase separation morphology, and ultimately enhance the power conversion efficiency (PCE) and stability of the PSCs. Specifically, the donor and acceptor illustrated a gradient-blended distribution in the sequential deposition-processed films, thus resulting in facilitated carrier characteristics in the gradient-blended devices. Consequently, the PSCs based on D18-Cl/Y6:ZY-4Cl have achieved a device efficiency of over 18% with the synergetic improvement of open-circuit voltage (VOC), short-circuit current density (JSC), and fill factor (FF). Therefore, this work reveals a facile approach to fabricating PSCs with improved performance and stability.

14.
Can J Ophthalmol ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38431271

RESUMO

OBJECTIVE: Ocular hypertension and uveitic glaucoma are important downstream sequela of noninfectious uveitis (NIU). Herein, we describe the clinical outcomes of NIU cases with ocular hypertension and uveitic glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: All adults (≥18 years) with NIU under the care of uveitis subspecialty tertiary care clinics between 2010 and 2021 were included. METHODS: The primary outcomes were baseline and final visual acuity. RESULTS: A total of 216 patients out of 914 (23.6%) cases with NIU had ocular hypertension or uveitic glaucoma over the study period. Of all patients with ocular hypertension or uveitic glaucoma, 46% were corticosteroid responders. Baseline and last median visual acuities were better for the ocular hypertension patients compared with patients with uveitic glaucoma (p < 0.001). A higher proportion of patients with uveitic glaucoma than patients with ocular hypertension required glaucoma surgery (p < 0.001). The regression analyses suggested that baseline visual acuity and anatomical classification are significant predictors of last visual acuity, whereas diagnosis of ocular hypertension versus uveitic glaucoma were significant predictors of requirement for glaucoma surgery (p < 0.001). CONCLUSION: A quarter of patients with NIU in this study developed ocular hypertension or uveitic glaucoma. Approximately half of the patients with ocular hypertension or uveitic glaucoma were deemed to be corticosteroid responders. Baseline and last visual acuity outcomes are better amongst ocular hypertension patients compared with those with uveitic glaucoma. Poor baseline visual acuity and panuveitis are predictors of worse vision at last follow-up. Additionally, diagnosis of uveitic glaucoma was a significant predictor of requirement for glaucoma surgery.

15.
Sci Transl Med ; 16(738): eadm8859, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478632

RESUMO

Engineered regulatory T (Treg) cells have emerged as precision therapeutics aimed at inducing immune tolerance while reducing the risks associated with generalized immunosuppression. This Viewpoint highlights the opportunities and challenges for engineered Treg cell therapies in treating autoimmune and other inflammatory diseases.


Assuntos
Doenças Autoimunes , Linfócitos T Reguladores , Humanos , Tolerância Imunológica , Terapia de Imunossupressão
16.
Zootaxa ; 5419(1): 53-84, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38480337

RESUMO

The 250 species of the second largest genus of Thysanoptera, Liothrips, are known as feeding mainly on green leaves, with many inducing galls or associated with galls. In China, 33 species are recognized including L. brevis sp. n., L. elongatus sp. n., L. longistylus sp. n., L. motuoensis sp. n., L. piceae sp. n., L. populi sp. n. and L. tibetanus sp. n., also seven species are recorded from this country for the first time. Four Hans Liothrips species are considered as new synonymies of L. vaneeckei that might be widespread in the Holarctic region. Three species are newly combined as Liothrips aporosae comb.n., Teuchothrips fuscus comb.n. and T. turkestanicus comb.n. The illustrated identification key to Chinese Liothrips species excludes L. hsuae but includes L. mirabilis due to its potential as a pest of Piper plants are growing throughout Southern China. Biology, structural variation, and generic relationships are also discussed.


Assuntos
Piper , Tisanópteros , Animais , China , Folhas de Planta
17.
Adv Sci (Weinh) ; 11(18): e2307136, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38445970

RESUMO

In this research, a 3D brain organoid model is developed to study POLG-related encephalopathy, a mitochondrial disease stemming from POLG mutations. Induced pluripotent stem cells (iPSCs) derived from patients with these mutations is utilized to generate cortical organoids, which exhibited typical features of the diseases with POLG mutations, such as altered morphology, neuronal loss, and mitochondiral DNA (mtDNA) depletion. Significant dysregulation is also identified in pathways crucial for neuronal development and function, alongside upregulated NOTCH and JAK-STAT signaling pathways. Metformin treatment ameliorated many of these abnormalities, except for the persistent affliction of inhibitory dopamine-glutamate (DA GLU) neurons. This novel model effectively mirrors both the molecular and pathological attributes of diseases with POLG mutations, providing a valuable tool for mechanistic understanding and therapeutic screening for POLG-related disorders and other conditions characterized by compromised neuronal mtDNA maintenance and complex I deficiency.


Assuntos
DNA Polimerase gama , Células-Tronco Pluripotentes Induzidas , Doenças Mitocondriais , Organoides , Organoides/metabolismo , Organoides/patologia , Humanos , DNA Polimerase gama/genética , DNA Polimerase gama/metabolismo , Doenças Mitocondriais/genética , Doenças Mitocondriais/metabolismo , Doenças Mitocondriais/patologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Mutação/genética , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Encéfalo/patologia , Encéfalo/metabolismo
18.
Front Neurol ; 15: 1355861, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38419708

RESUMO

Purpose: Pyridoxine-dependent epilepsy due to ALDH7A1 variants (PDE-ALDH7A1) is a rare disorder, presenting typically with severe neonatal, epileptic encephalopathy. Early diagnosis is imperative to prevent uncontrolled seizures. We have explored the role of EEG in the diagnosis and management of PDE. Methods: A total of 13 Norwegian patients with PDE-ALDH7A1 were identified, of whom five had reached adult age. Altogether 163 EEG recordings were assessed, 101 from the 1st year of life. Results: Median age at seizure onset was 9 h (IQR 41), range 1 h-6 days. Median delay from first seizure to first pyridoxine injection was 2 days (IQR 5.5). An EEG burst suppression pattern was seen in eight patients (62%) during the first 5 days of life. Eleven patients had recordings during pyridoxine injections: in three, immediate EEG improvement correlated with seizure control, whereas in six, no change of epileptiform activity occurred. Of these six, one had prompt clinical effect, one had delayed effect (< 1 day), one had no effect, one had uncertain effect, and another had more seizures. A patient without seizures at time of pyridoxine trial remained seizure free for 6 days. Two patients with prompt clinical effect had increased paroxysmal activity, one as a conversion to burst suppression. Autonomic seizures in the form of apnoea appeared to promote respiratory distress and were documented by EEG in one patient. EEG follow-up in adult age did not show signs of progressing encephalopathy. Conclusion: A neonatal burst suppression EEG pattern should raise the suspicion of PDE-ALDH7A1. Respiratory distress is common; isolated apnoeic seizures may contribute. EEG responses during pyridoxine trials are diverse, often with poor correlation to immediate clinical effect. Reliance on single trials may lead to under-recognition of this treatable condition. Pyridoxine should be continued until results from biomarkers and genetic testing are available.

20.
Histopathology ; 84(7): 1192-1198, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38409850

RESUMO

BACKGROUND: Carcinomas of the seminal vesicle are exceedingly rare, with a limited number of cases described in the literature. Reported cases span a relatively wide morphological spectrum, and their genomic features remain unexplored. DESIGN: In this study, we interrogated five primary epithelial neoplasms of the seminal vesicle using a targeted DNA sequencing platform (OncoPanel, 447 genes). RESULTS: The tumours included one adenocarcinoma with intestinal phenotype presenting after external beam radiation (for prostatic adenocarcinoma), one carcinoma with Müllerian-type clear cell phenotype, two mucinous tumours resembling low-grade mucinous neoplasms of the appendix (LAMN) and one mucinous cystadenoma. The post-radiation mucinous adenocarcinoma had genomic findings consistent with bi-allelic inactivation of TP53, as well as multiple copy-number changes with regional and chromosomal arm-level copy-number losses. The Müllerian-type clear cell carcinoma exhibited a complex copy-number profile with numerous regional and arm-level copy-number changes, as well as focal amplification events, including copy-number gain of 8q and amplification of a region within 20q13. Both low-grade mucinous tumours resembling LAMN harboured hot-spot gain-of-function KRAS variants (p.G12V and p.G13D) as the only genomic alteration. No genomic alterations were detected inthe lesion diagnosed as mucinous cystadenoma. CONCLUSION: Our results suggest that primary low-grade mucinous neoplasms of the seminal vesicle may represent a distinct entity equivalent to appendiceal counterparts, driven by gain-of-function variants of RAS GTPases. The remaining tumours showed genomic features that closely resembled those of neoplasms with comparable phenotypes and/or biological characteristics arising in other sites, suggesting that they could be managed similarly, with special considerations related to their anatomical location.


Assuntos
Neoplasias Císticas, Mucinosas e Serosas , Neoplasias Epiteliais e Glandulares , Glândulas Seminais , Humanos , Masculino , Adulto , Idoso , Adulto Jovem , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas p21(ras)/genética , Glândulas Seminais/patologia , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/patologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Cistadenoma Mucinoso/genética , Cistadenoma Mucinoso/patologia , Neoplasias Císticas, Mucinosas e Serosas/genética , Neoplasias Císticas, Mucinosas e Serosas/patologia
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