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1.
J Rheum Dis ; 31(2): 125-129, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38559795

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hematological disorder characterized by uncontrolled activation of CD8+ T and natural killer cells, leading to a cytokine storm and severe organ dysfunction. Although secondary HLH related to autoimmune diseases usually demonstrates a good treatment response to immunosuppressive therapy for underlying conditions, there is no consensus regarding the treatment in case of unresponsiveness to the treatment. Herein, we present a case of HLH that was unresponsive to high-dose glucocorticoid and cyclosporine treatment in a patient with newly diagnosed systemic lupus erythematosus. The patient's clinical features and laboratory abnormalities rapidly improved with ruxolitinib, an oral Janus kinase 1 and 2 (JAK1/2) inhibitor. This result suggests that blocking JAK-STAT pathway may be a potential treatment option in patients with refractory HLH secondary to autoimmune diseases.

2.
Biomater Res ; 28: 0012, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560578

RESUMO

Non-biodegradable implants have undergone extensive investigation as drug delivery devices to enable advanced healthcare toward personalized medicine. However, fibroblast encapsulation is one of the major challenges in all non-biodegradable implants, besides other challenges such as high initial burst, risk of membrane rupture, high onset time, non-conformal contact with tissues, and tissue damage. To tackle such challenges, we propose a novel ultrasoft and flexible balloon-type drug delivery device for unidirectional and long-term controlled release. The ultrasoft balloon-type device (USBD) was fabricated by using selective bonding between 2 polydimethylsiloxane (PDMS) membranes and injecting a fluid into the non-bonded area between them. The balloon acted as a reservoir containing a liquid drug, and at the same time, the membrane of the balloon itself acted as the pathway for release based on diffusion. The release was modulated by tuning the thickness and composition of the PDMS membrane. Regardless of the thickness and composition, all devices exhibited zero-order release behavior. The longest zero-order release and nearly zero-order release were achieved for 30 days and 58 days at a release rate of 1.16 µg/day and 1.68 µg/day, respectively. In vivo evaluation was performed for 35 days in living rats, where the USBD maintained zero-order and nearly zero-order release for 28 days and 35 days, respectively. Thanks to the employment of ultrasoft and flexible membranes and device design, the USBD could achieve minimal tissue damage and foreign body responses. It is expected that the proposed device may provide a novel approach for long-term drug delivery with new therapeutic modalities.

3.
Clin Orthop Surg ; 16(2): 286-293, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38562630

RESUMO

Background: Radiation therapy (RT) performed before anterior cervical spine surgery (ACSS) may cause fascial plane fibrosis, decreased soft-tissue vascularity, and vertebral body weakness, which could increase the risk of esophageal and major vessel injuries, wound complications, and construct subsidence. Therefore, this study aimed to evaluate whether preoperative RT performed for metastatic spine cancer (MSC) at the cervical spine increases perioperative morbidity for ACSS. Methods: Forty-nine patients who underwent ACSS for treatment of MSC at the cervical spine were retrospectively reviewed. All the patients underwent anterior cervical corpectomy via the anterior approach. Patient demographics, surgical factors, operative factors, and complications were recorded. Results of patients who were initially treated with RT before ACSS (RT group) were compared with those who did not receive RT before ACSS (non-RT group). Results: Eighteen patients (36.7%) were included in the RT group, while the remaining 31 (63.3%) were included in the non-RT group. Surgery-related factors, including operation time (p = 0.109), estimated blood loss (p = 0.246), amount of postoperative drainage (p = 0.604), number of levels operated (p = 0.207), and number of patients who underwent combined posterior fusion (p = 0.768), did not significantly differ between the 2 groups. Complication rates, including esophageal injury, dural tear, infection, wound dehiscence, and mechanical failure, did not significantly differ between the RT and non-RT groups. Early subsidence was significantly greater in the non-RT group compared to that in the RT group (p = 0.012). Conclusions: RT performed before surgery for MSC does not increase the risk of wound complication, mechanical failure, or vital structure injury during ACSS. The surgical procedural approach was not complicated by previous RT history. Therefore, surgeons can safely choose the anterior approach when the number of levels or location of MSC favors anterior surgery, and performing a posterior surgery is unnecessary due to a concern that previous RT may increase complication rates of ACSS.


Assuntos
Neoplasias Ósseas , Fusão Vertebral , Humanos , Estudos Retrospectivos , Vértebras Cervicais/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fusão Vertebral/métodos
4.
Nanoscale Horiz ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563255

RESUMO

As the downscaling of conventional dynamic random-access memory (DRAM) has reached its limits, 3D DRAM has been proposed as a next-generation DRAM cell architecture. However, incorporating silicon into 3D DRAM technology faces various challenges in securing cost-effective high cell transistor performance. Therefore, many researchers are exploring the application of next-generation semiconductor materials, such as transition oxide semiconductors (OSs) and metal dichalcogenides (TMDs), to address these challenges and to realize 3D DRAM. This study provides an overview of the proposed structures for 3D DRAM, compares the characteristics of OSs and TMDs, and discusses the feasibility of employing the OSs and TMDs as the channel material for 3D DRAM. Furthermore, we review recent progress in 3D DRAM using the OSs, discussing their potential to overcome challenges in silicon-based approaches.

5.
J Transl Med ; 22(1): 323, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561750

RESUMO

BACKGROUND: MicroRNA (miRNA)-21-5p participates in various biological processes, including cancer and autoimmune diseases. However, its role in the development of fibrosis in the in vivo model of systemic sclerosis (SSc) has not been reported. This study investigated the effects of miRNA-21a-5p overexpression and inhibition on SSc fibrosis using a bleomycin-induced SSc mouse model. METHODS: A murine SSc model was induced by subcutaneously injecting 100 µg bleomycin dissolved in 0.9% NaCl into C57BL/6 mice daily for 5 weeks. On days 14, 21, and 28 from the start of bleomycin injection, 100 µg pre-miRNA-21a-5p or anti-miRNA-21a-5p in 1 mL saline was hydrodynamically injected into the mice. Fibrosis analysis was conducted in lung and skin tissues of SSc mice using hematoxylin and eosin as well as Masson's trichrome staining. Immunohistochemistry was used to examine the expression of inflammatory cytokines, phosphorylated signal transducer and activator of transcription-3 (STAT3) at Y705 or S727, and phosphatase and tensin homologue deleted on chromosome-10 (PTEN) in skin tissues of SSc mice. RESULTS: MiRNA-21a-5p overexpression promoted lung fibrosis in bleomycin-induced SSc mice, inducing infiltration of cells expressing TNF-α, IL-1ß, IL-6, or IL-17, along with STAT3 phosphorylated cells in the lesional skin. Conversely, anti-miRNA-21a-5p injection improved fibrosis in the lung and skin tissues of SSc mice, reducing the infiltration of cells secreting inflammatory cytokines in the skin tissue. In particular, it decreased STAT3-phosphorylated cell infiltration at Y705 and increased the infiltration of PTEN-expressing cells in the skin tissue of SSc mice. CONCLUSION: MiRNA-21a-5p promotes fibrosis in an in vivo murine SSc model, suggesting that its inhibition may be a therapeutic strategy for improving fibrosis in SSc.


Assuntos
MicroRNAs , Escleroderma Sistêmico , Animais , Camundongos , Bleomicina , Citocinas/metabolismo , Modelos Animais de Doenças , Fibrose , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/induzido quimicamente , Pele/patologia
6.
Sci Rep ; 14(1): 7787, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565933

RESUMO

This retrospective study aimed to determine risk factors associated with post-operative bleeding after dentoalveolar surgery in patients taking anticoagulants. Patients taking anticoagulants who were planned to undergo periodontal flap operation, tooth extraction or implant surgery were included. Patients were divided into two subgroups according to the maintenance of anticoagulants following medical consultation: (1) maintenance group and (2) discontinuation group. The analysed patient-related factors included systemic diseases, maintenance of anticoagulants and types of anticoagulant. Intra- and post-operative treatment-related factors, haemostatic methods and post-operative bleeding were collected for statistical analyses. There were 35 post-operative bleeding complications (6.5%) in the 537 included patients: 21 (8.6%) in maintenance group and 14 (4.8%) in discontinuation group. The type of anticoagulant (p = 0.037), tooth extraction combined with bone grafting (p = 0.016) and type of implant surgery (p = 0.032) were significantly related to the post-operative bleeding rate. In the maintenance group, atrial fibrillation [odds ratio (OR) = 6.051] and vitamin K inhibitors (OR = 3.679) were associated with a significantly higher bleeding risk. From this result, it can be inferred that the decision to continue anticoagulants should be made carefully based on the types of anticoagulant and the characteristics of dentoalveolar surgeries performed: extraction with bone grafting, multiple implantations and involvement of maxillary arch.


Assuntos
Anticoagulantes , Fibrilação Atrial , Humanos , Anticoagulantes/efeitos adversos , Estudos de Coortes , Estudos Retrospectivos , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/induzido quimicamente , Extração Dentária/efeitos adversos , Fibrilação Atrial/complicações , Administração Oral
7.
Biol Psychiatry ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38575105

RESUMO

BACKGROUND: Major depression and anxiety disorder are significant causes of disability and socio-economic burden. Despite the prevalence and considerable impact of these affective disorders, their pathophysiology remains elusive. Thus, there is an urgent need to develop novel therapeutics for these conditions. We evaluated the role of SIRT1 in regulating dysfunctional processes of reward by using chronic social defeat stress (CSDS) to induce depression- and anxiety-like behaviors. CSDS induces physiological and behavioral changes that recapitulate depression-like symptomatology and alters gene expression programs in the nucleus accumbens, yet cell type-specific changes in this critical structure remain largely unknown. METHODS: We examined transcriptional profiles of D1-MSNs lacking deacetylase activity of SIRT1 by RNA sequencing (RNA-Seq) in a cell-type specific manner using the RiboTag line of mice. We analyzed differentially expressed genes using gene ontology tools including SynGO and EnrichR, and further demonstrated functional changes in D1-MSN specific SIRT1-KO mice using electrophysiological and behavioral measurements. RESULTS: RNAseq revealed altered transcriptional profiles of D1-MSNs lacking functional SIRT1 and showed specific changes in synaptic genes including glutamatergic and GABAergic receptors in D1-MSNs. These molecular changes may be associated with decreased excitatory and increased inhibitory neural activity in Sirt1-KO D1-MSNs, accompanied by morphological changes. Moreover, the D1-MSN-specific Sirt1-KO mice exhibited pro-resilient changes in anxiety- and depression-like behaviors. CONCLUSIONS: SIRT1 coordinates excitatory and inhibitory synaptic genes to regulate GABAergic output tone of D1-MSNs. These findings reveal a novel signaling pathway that has the potential for the development of innovative treatments for affective disorders.

8.
ANZ J Surg ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597171

RESUMO

We report two cases of total gastrectomy and Roux-en-Y reconstruction that required future endoscopic surveillance of the duodenum. As such, an additional proximal duodenojejunostomy was fashioned to facilitate endoscopic surveillance.

9.
J Esthet Restor Dent ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38591169

RESUMO

OBJECTIVES: To evaluate clinical, clinician- and patient-reported outcomes (PROs) of two adjacent single posterior implants immediately loaded with definitive single crowns up to 1 year. Ten patients in need of two adjacent posterior single implants were included. All implants were placed applying a fully digital workflow. Definitive screw-retained single zirconia crowns were delivered within 72 h after implant placement. Clinical parameters, patient- and clinician-reported outcomes were assessed up to 1 year of follow-up. CLINICAL CONSIDERATIONS: Clinical outcomes remained stable, with no implant failures or technical and biological complications throughout the observation period. Patient satisfaction was very high at baseline (crown delivery) and remained consistently high at 6 and 12 months of follow-up. Crown insertion 3 days after implant placement was rated as an easy procedure by clinicians. CONCLUSIONS: Two adjacent single implants with immediate definitive restorations (<72 h) in the posterior region appear to be a viable and easy treatment option to shorten the overall treatment time and potentially enhancing patient satisfaction. However, randomized controlled trials are needed to confirm the advantages of this treatment protocol over a delayed loading approach. CLINICAL SIGNIFICANCE: In selected cases, immediate implant loading with definitive restorations in the posterior region appears a valuable and straightforward option to shorten the overall treatment time.

10.
ACS Appl Mater Interfaces ; 16(13): 16553-16562, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570940

RESUMO

In this study, two novel multiple resonance (MR) emitters, DtCzBN and Cy-DtCzBN, were designed based on the well-known BCzBN structure and synthesized for narrowband solution-processed organic light-emitting diodes (OLEDs). Cy-DtCzBN possesses a dimeric V-shaped structure formed by coupling two individual DtCzBN units via a nonconjugated cyclohexane linker. When compared with DtCzBN, Cy-DtCzBN, as a medium-sized molecule, was found to maintain the optical and photophysical properties of the corresponding monomeric unit, DtCzBN, but exhibits high thermal stability, excellent solubility, and good film-forming ability. Additionally, solution-processed OLEDs were fabricated by using two sets of molecules: one set of small molecular hosts and emitters (i.e., mCP and DtCzBN) and the other set of medium-sized molecular hosts and emitters (i.e., Cy-mCP and Cy-DtCzBN). Notably, devices using medium-sized molecular hosts and emitters exhibited similar optical and photophysical properties but showed significantly improved reproducibility and thermal stability compared with those based on small molecular hosts and emitters. Our current study provides some insights into molecular design strategies for thermally stable hosts and emitters, which are highly suitable for solution-processed OLEDs.

11.
Psychiatry Investig ; 21(3): 294-299, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38569587

RESUMO

OBJECTIVE: To date, early detection of mild cognitive impairment (MCI) has mainly depended on paper-based neuropsychological assessments. Recently, biomarkers for MCI detection have gained a lot of attention because of the low sensitivity of neuropsychological assessments. This study proposed the functional near-infrared spectroscopy (fNIRS)-derived data with convolutional neural networks (CNNs) to identify MCI. METHODS: Eighty-two subjects with MCI and 148 healthy controls (HC) performed the 2-back task, and their oxygenated hemoglobin (HbO2) changes in the prefrontal cortex (PFC) were recorded during the task. The CNN model based on fNIRS-derived spatial features with HbO2 slope within time windows was trained to classify MCI. Thereafter, the 5-fold cross-validation approach was used to evaluate the performance of the CNN model. RESULTS: Significant differences in averaged HbO2 values between MCI and HC groups were found, and the CNN model could better discriminate MCI with over 89.57% accuracy than the Korean version of the Montreal Cognitive Assessment (MoCA) (89.57%). Specifically, the CNN model based on HbO2 slope within the time window of 20-60 seconds from the left PFC (96.09%) achieved the highest accuracy. CONCLUSION: These findings suggest that the fNIRS-derived spatial features with CNNs could be a promising way for early detection of MCI as a surrogate for a conventional screening tool and demonstrate the superiority of the fNIRS-derived spatial features with CNNs to the MoCA.

12.
Clin Auton Res ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652421

RESUMO

PURPOSE: The specific characteristics of autonomic involvement in patients with early Parkinson's disease (PD) are unclear. This study aimed to evaluate the characteristics of autonomic dysfunction in drug-naïve patients with early-stage PD without orthostatic hypotension (OH) by analyzing Valsalva maneuver (VM) parameters. METHODS: We retrospectively analyzed drug-naïve patients without orthostatic hypotension (n = 61) and controls (n = 20). The patients were subcategorized into early PD (n = 35) and mid-PD (n = 26) groups on the basis of the Hoehn and Yahr staging. VM parameters, including changes in systolic blood pressure at late phase 2 (∆SBPVM2), ∆HRVM3, Valsalva ratio (VR), pressure recovery time, adrenergic baroreflex sensitivity, and vagal baroreflex sensitivity, were assessed. RESULTS: In the early PD group, ∆SBPVM2, a marker of sympathetic function, was significantly lower compared with that in controls (risk ratio = 0.95, P = 0.027). Receiver operating characteristic (ROC) curve analysis showed an optimal cut-off value of -10 mmHg for ∆SBPVM2 [P = 0.002, area under the curve (AUC): 0.737]. VR exhibited an inverse relationship with Unified Parkinson's Disease Rating Scale Part 3 scores in the multivariable regression analysis (VR: P = 0.038, ß = -28.61), whereas age showed a positive relationship (age: P = 0.027, ß = 0.35). CONCLUSION: The ∆BPVM2 parameter of the VM may help detect autonomic nervous system involvement in early-PD without OH. Our results suggest that sympathetic dysfunction is an early manifestation of autonomic dysfunction in patients with PD.

13.
Nutrients ; 16(7)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38613064

RESUMO

Panax ginseng fruit is known to have various biological effects owing to its large amount of saponins such as ginsenosides. In the present study, ginseng berry juice was confirmed to be effective against acute inflammation. Ginseng berry juice was used for analysis of active constituents, antioxidant efficacy, and in vivo inflammation. A high-performance liquid chromatography method was used for analysis of ginsenosides. In an HCl/ethanol-induced acute gastric injury model, microscopic, immunofluorescent, and immunohistochemical techniques were used for analysis of inhibition of gastric injury and mechanism study. In a mouse model of acute gastritis induced with HCl/ethanol, ginseng berry juice (GBJ, 250 mg/kg) showed similar gastric injury inhibitory effects as cabbage water extract (CB, 500 mg/kg, P.O). GBJ dose-dependently modulated the pro-inflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), and Interleukin-13 (IL-13). GBJ inhibited the activation of Nuclear Factor kappa bB (NF-κB) and suppressed the expressions of cyclooxigenase-2 (COX-2) and prostaglandin 2 (PGE2). The anti-inflammatory effect of GBJ is attributed to ginsenosides which have anti-inflammatory effects. Productivity as an effective food source for acute gastritis was analyzed and showed that GBJ was superior to CB. In addition, as a functional food for suppressing acute ulcerative symptoms, it was thought that the efficacy of gastric protection products would be higher if GBJ were produced in the form of juice rather than through various extraction methods.


Assuntos
Gastrite , Ginsenosídeos , Panax , Animais , Camundongos , Frutas , Ginsenosídeos/farmacologia , Inflamação/tratamento farmacológico , Etanol , Anti-Inflamatórios/farmacologia
14.
RMD Open ; 10(2)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38599651

RESUMO

OBJECTIVE: Primary Sjögren's syndrome (pSS) is the second most common chronic autoimmune connective tissue disease. Autoantibodies, immunoglobulin (IgG) anti-SSA/Ro, in serum is a key diagnostic feature of pSS. Since pSS is a disease of the salivary gland, we investigated anti-SSA/Ro52 in saliva. METHODS: Using a novel electrochemical detection platform, Electric Field-Induced Release and Measurement, we measured IgG/M/A, IgG, IgA, IgA isotypes (IgA1 and IgA2) and IgA1 subclasses (polymeric and monomeric IgA1) to anti-SSA/Ro52 in saliva supernatant of 34 pSS, 35 dry eyes and dry mouth (patients with Sicca) and 41 health controls. RESULTS: Saliva IgG/M/A, IgG, IgA, IgA isotypes and IgA1 subclasses to anti-SSA/Ro52 differed significantly between pSS, non-pSS Sicca and healthy subjects. Elevated monomeric IgA1 was observed in patients with non-pSS Sicca while elevated polymeric IgA1 (pIgA1) was observed in patients with pSS. Salivary polymeric but not monomeric IgA1 (mIgA1) isoform correlated with focus score (r2=0.467, p=0.001) CONCLUSIONS: Salivary anti-Ro52 polymeric IgA1 isoform is associated with glandular inflammation in pSS, while salivary monomeric IgA1 is associated with Sicca. Whether IgA1 isotope switching plays a role in the progression of the Sicca to pSS warrants further investigation.


Assuntos
Saliva , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/diagnóstico , Imunoglobulina A , Autoanticorpos , Imunoglobulina G
15.
Sci Rep ; 14(1): 8749, 2024 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627423

RESUMO

The fighter pilots exposed to high gravitational (G) acceleration must perform anti-G maneuvers similar to the Valsalva maneuver. However, the effects of high-G acceleration and anti-G maneuvers on cardiac function have rarely been studied. This study aimed to investigate the effects of high-G forces on cardiac function of fighter pilots. Fighter pilots who underwent regular health check-ups and echocardiography were included (n = 29; 100% men, 41 ± 10 years old; mean flight time, 1821 ± 1186 h). Trainees who had not experienced any flights were included in the control group (n = 16; 100% men, 36 ± 17 years old). Echocardiographic data included left ventricular chamber size, systolic and diastolic functions, right ventricular systolic pressure (RVSP), inferior vena cava (IVC) collapsibility, and tricuspid annular plane systolic excursion (TAPSE). No significant differences in left ventricular ejection fraction, RVSP, or IVC collapsibility were observed between two groups. In the multivariate linear regression analysis with total flight time as an independent continuous variable for fighter pilots, TAPSE was positively correlated with total flight time. The experience of fighter pilots who were exposed to high-G acceleration forces and anti-G maneuvers did not cause cardiac structural changes, but the exposure might be associated with right heart function changes.


Assuntos
Hipergravidade , Pilotos , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Feminino , Volume Sistólico , Função Ventricular Esquerda , Hipergravidade/efeitos adversos , Aceleração
16.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167168, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38641012

RESUMO

OBJECTIVES: Testing for anti-SSA/Ro antibodies in serum is essential in the diagnostic work-up for primary Sjögren's syndrome (pSS). In this study, we aimed to validate our previous assay for detection of salivary anti-SSA/Ro52, and to develop assays for detection of salivary anti-SSA/Ro60 and for detection of anti-Ro52 and -Ro60 in plasma using the electric field-induced release and measurement (EFIRM) platform. METHODS: Whole saliva samples from two independent Danish cohorts (DN1 and DN2) including 49 patients with pSS, 73 patients with sicca symptoms, but not fulfilling the classification criteria for pSS (non-pSS sicca), and 51 healthy controls (HC), as well as plasma samples from the DN1 cohort were analyzed using EFIRM to detect anti-SSA/Ro52 and -Ro60. RESULTS: In the DN1 cohort, 100 % in the pSS group and 16 % in the non-pSS sicca group were serum anti-SSA/Ro positive by ELISA. EFIRM detected anti-SSA (Ro52 and/or -Ro60) in plasma and saliva in 100 % and 96 % patients with pSS, and 16 % and 29 % with non-pSS sicca. In the DN2 cohort, 80 % patients with pSS and 26 % with non-pSS sicca were serum anti-SSA/Ro positive. Salivary anti-SSA discriminated patients with pSS from HC and non-pSS sicca with an AUC range of 0.74-0.96 in the DN1 and DN2 cohorts. EFIRM discriminated pSS from non-pSS sicca with an AUC of 0.98 in plasma. CONCLUSION: Our findings suggest that salivary anti-SSA/Ro antibodies are potential discriminatory biomarkers for pSS, which may also identify seronegative patients, addressing the unmet clinical need of early detection and stratification of pSS.

17.
Prog Neurobiol ; : 102612, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38642602

RESUMO

Recurrent seizures lead to accumulation of the activity-dependent transcription factor ∆FosB in hippocampal dentate granule cells in both mouse models of epilepsy and mouse models of Alzheimer's disease (AD), which is also associated with increased incidence of seizures. In patients with AD and related mouse models, the degree of ∆FosB accumulation corresponds with increasing severity of cognitive deficits. We previously found that ∆FosB impairs spatial memory in mice by epigenetically regulating expression of target genes such as calbindin that are involved in synaptic plasticity. However, the suppression of calbindin in conditions of neuronal hyperexcitability has been demonstrated to provide neuroprotection to dentate granule cells, indicating that ∆FosB may act over long timescales to coordinate neuroprotective pathways. To test this hypothesis, we used viral-mediated expression of ∆JunD to interfere with ∆FosB signaling over the course of several months in transgenic mice expressing mutant human amyloid precursor protein (APP), which exhibit spontaneous seizures and develop AD-related neuropathology and cognitive deficits. Our results demonstrate that persistent ∆FosB activity acts through discrete modes of hippocampal target gene regulation to modulate neuronal excitability, limit recurrent seizure activity, and provide neuroprotection to hippocampal dentate granule cells in APP mice.

18.
World J Mens Health ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38606860

RESUMO

PURPOSE: Identifying and managing risk factors for lower urinary tract symptoms (LUTS) is crucial because it impacts the quality of life of elderly individuals. Lifestyle factors, including physical activity (PA), and their relationship with LUTS have not been well studied. This objective of this study was to investigate the association between PA and LUTS. MATERIALS AND METHODS: A total of 7,296 men were included in this cross-sectional study. PA was quantified in metabolic equivalent (MET)-hours per week, and LUTS severity was assessed using the international prostate symptom score. Logistic regression was used to analyze the association between PA and LUTS, including voiding and storage symptoms. RESULTS: The average age of the participants was 57.8 years, and the prevalence of LUTS was 41.3%. After adjusting for potential confounders, PA was inversely associated with the prevalence and severity of moderate-to-severe LUTS, showing a dose-response pattern (all p for trend <0.01). Compared to the minimal activity group, which engaged in <5 MET-hours per week of PA, the odds ratios for moderate to severe LUTS were 0.83 (95% confidence interval [CI]: 0.72-0.97) for men engaging in 15-30 MET-hours per week, 0.82 (95% CI: 0.71-0.95) for 30-60 MET-hours per week, and 0.72 (95% CI: 0.62-0.84) for ≥60 MET-hours per week. The possible protective effect of PA was still observed in the additional analysis for voiding and storage symptoms showing the same dose-response pattern (all p for trend <0.01). CONCLUSIONS: A higher PA level was associated with a lower prevalence and severity of total, voiding, and storage LUTS in a dose-dependent manner in Korean men.

19.
World Neurosurg ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38608818

RESUMO

BACKGROUND: Patients with Lumbar Spinal Stenosis (LSS) typically complain of back pain and leg pain. These symptoms reduce the quality of life and also cause sleep disturbances. This study compares pregabalin and limaprost's efficacy in LSS for pain, disability, quality of life, and sleep, aiming to offer insights for medication selection. METHODS: This study was designed as a prospective, randomized, single-center, single-blinded, clinical superiority trial targeting patients with LSS. For 6 weeks, 111 patients per group were administered medication following a standard regimen, after which patient-reported outcomes were measured. The primary outcome was the Visual Analogue Scale (VAS) for back and leg pain, and the secondary outcomes included the Oswestry Disability Index (ODI), European Quality of Life 5 Dimensions (EQ-5D), and sleep quality. RESULTS: After 6 weeks of medication, there were significant improvements over time in the primary outcome, VAS for back pain and leg pain, in both groups, but no significant difference between the two groups. Similarly, for the secondary outcomes, ODI and EQ-5D, both groups showed significant improvements, yet there was no significant difference between them. In the subgroup analysis targeting poor sleepers (Pittsburgh sleep quality index, PSQI > 5), both groups also exhibited significant improvements in sleep quality, but again, there was no significant difference between the groups. CONCLUSIONS: Efficacy of pregabalin, limaprost in back and leg pain, ODI, EQ-5D, and sleep quality, but there was no significant difference between the two groups. Thus, it is advisable to prescribe based on individual drug responses and potential complications.

20.
Neurol Sci ; 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613590

RESUMO

BACKGROUND AND PURPOSE: Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disorder characterized by myotonia and progressive muscle weakness. Beyond the primary symptoms, there is growing concern regarding a higher incidence of certain comorbidities in DM1 patients, including cancer, diabetes, thyroid dysfunction, and cataracts. This study was designed to examine the occurrence of these conditions among patients diagnosed with DM1 in South Korea, using data from the National Health Insurance Service database. METHODS: The study undertook a comprehensive review of 3,842 patients diagnosed with DM1 between 2012 and 2018. We assessed the incidence of cancer and the prevalence of diabetes, thyroid dysfunction, and cataracts among these patients, comparing their rates to those in the general population. RESULTS: In the study cohort, 463 out of 3,842 DM1 patients (12.04%) were diagnosed with cancer, indicating a substantial elevation in cancer risk with an overall standard incidence ratio of 1.9 (95% CI = 1.6-2.3, p < 0.01) when compared to the expected rates in the general population. Moreover, the prevalence of diabetes (15.2%) and thyroid dysfunction (17.6%) was noteworthy in the DM1 population. The mean age at which DM1 patients underwent cataract surgery was 55.07 years, noticeably younger than the mean age of 69.25 years for cataract surgery in the general population. CONCLUSIONS: DM1 patients have a noteworthy occurrence of several comorbidities such as cancer, diabetes, thyroid dysfunction, and earlier cataract surgery. This highlights the importance of a comprehensive and integrative approach to the management and treatment of DM1, going beyond addressing only the primary neuromuscular symptoms. More research is required to understand the underlying mechanisms contributing to these comorbidities in DM1 patients, which may inform preventative measures and guide improvements in patient care.

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