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1.
Heliyon ; 10(9): e30023, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38726131

RESUMO

Primary spontaneous pneumothorax (PSP) primarily affects slim and tall young males. Exploring the etiological link between chest wall structural characteristics and PSP is crucial for advancing treatment methods. In this case-control study, chest computed tomography (CT) images from patients undergoing thoracic surgery, with or without PSP, were analyzed using Artificial Intelligence. Convolutional Neural Network (CNN) model of EfficientNetB3 and InceptionV3 were used with transfer learning on the Imagenet to compare the images of both groups. A heatmap was created on the chest CT scans to enhance interoperability, and the scale-invariant feature transform (SIFT) was adopted to further compare the image level. A total of 2,312 CT images of 26 non-PSP patients and 1,122 CT images of 26 PSP patients were selected. Chest-wall apex pit (CAP) was found in 25 PSP and three non-PSP patients (p < 0.001). The CNN achieved a testing accuracy of 93.47 % in distinguishing PSP from non-PSP based on chest wall features by identifying the existence of CAP. Heatmap analysis demonstrated CNN's precision in targeting the upper chest wall, accurately identifying CAP without undue influence from similar structures, or inappropriately expanding or minimizing the test area. SIFT results indicated a 10.55 % higher mean similarity within the groups compared to between PSP and non-PSP (p < 0.001). In conclusion, distinctive radiographic chest wall configurations were observed in PSP patients, with CAP potentially serving as an etiological factor linked to PSP. This study accentuates the potential of AI-assisted analysis in refining diagnostic approaches and treatment strategies for PSP.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38733124

RESUMO

INTRODUCTION: Chronic spontaneous urticaria (CSU) poses significant challenges, especially in pediatric and adolescent patients, impacting physical, emotional, and social well-being. Recent biologic breakthroughs offer promise, however, data on safety and efficacy in this population remain limited. AREAS COVERED: This review examines current biologic treatments in pediatrics and adolescents with CSU and explores the rapidly emerging landscape. EXPERT OPINION: Despite omalizumab's approval for allergic asthma in children since 2009, its delayed approval for CSU raises questions. Ligelizumab, a next-generation anti-IgE mAb, showed effectiveness in adults but lacks pediatric studies. CT-P39, a biosimilar to omalizumab, demonstrates promise, yet adolescent-specific outcomes are undisclosed. Dupilumab's recent approval for atopic dermatitis in children from 6 months onwards signifies progress. Expert opinion underscores the scarcity of controlled trials in pediatric and adolescent CSU, emphasizing the need for comprehensive studies. Age-specific data and collaboration are crucial for addressing research gaps and expanding indications for pediatric CSU treatment. The recently validated UAS7 parameter in children marks a milestone for prospective clinical trials. Despite challenges, the biology therapy outlook for pediatric and adolescent CSU is promising. Importantly, studies indicate that pediatric CSU is at least as prevalent as in adults, highlighting the need for approved treatments in this population.

3.
Acta Paediatr ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733138

RESUMO

AIM: To assess testicular volume at puberty for boys who underwent orchidopexy at 9 or at 36 months compared to boys with spontaneous postnatal descent. METHODS: At age 6 months, boys with congenital unilateral cryptorchidism were randomised to surgery at 9 or 39 months of age and followed to 16 years in parallel with boys with spontaneous postnatal descent. Ultrasound was done at 11 and 16 years to determine testicular volume. The ratio of the initially undescended testis to its scrotal counterpart was used to assess testicular growth. RESULTS: At age 16, the ratio was lower (p < 0.00) in the late group compared to the early group. At 16 years, the spontaneously descended testes were significantly smaller than their scrotal counterparts but larger than the operated groups (early p < 0.01 and late p < 0.00). CONCLUSION: Our data at 16 years show that orchidopexy at 9 months results in better testicular growth compared to 3 years but did not reach the corresponding volumes of their scrotal counterparts. This indicates that earlier surgery is beneficial to testicular growth. At age 16, the postnatally descended testes were not only larger than the surgically treated testes but also exhibited impaired testicular growth.

4.
Indian J Surg Oncol ; 15(2): 370-374, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38741637

RESUMO

Sarcomatoid hepatocellular carcinoma is a rare histologic variant of primary liver cancer comprising of malignant spindle cells and typical hepatocellular carcinoma (HCC). In terms of clinical presentation, they usually exhibit extensive tumor burden due to their larger size and a metastatic disease at the time of diagnosis as compared to conventional HCC. Tumor lysis syndrome is an oncological emergency, usually seen after cytotoxic chemotherapy in haematological malignancies. Here, we highlight a case of 76-year old male with no comorbidities, presenting with an excruciating backache and a paravertebral soft tissue mass and multiple osteolytic lesions, was clinically suspected to be a plasma cell neoplasm. On further evaluation, the patient was diagnosed of a sarcomatoid variant of hepatocellular carcinoma. This report showcases multiple rare findings by the presence of non-specific symptoms, non-cirrhotic liver, normal serum alpha protein levels and the occurrence of a spontaneous tumor lysis syndrome in a solid malignancy.

5.
Infect Drug Resist ; 17: 1803-1810, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741944

RESUMO

Background: Gordonia terrae is an opportunistic pathogen that rarely causes clinical infections. Here, we first report a case of spontaneous bacterial peritonitis in patients with hepatitis C cirrhosis caused by Gordonia terrea. Case Presentation: A 71-year-old male patient was diagnosed with spontaneous bacteria peritonitis secondary to hepatitis C cirrhosis. The result of bacterial culture in ascites was positive, and the pathogenic bacteria was preliminarily identified as the Gordonia genus by matrix-assisted laser desorption ionization-time of flight mass spectrometry. After 16S rRNA sequencing analysis, it was determined to be the Gordonia terrea. Symptoms relieved after treatment with ceftazidime. Conclusion: This case indicates that the clinical infections caused by Gordonia terrea should be brought to the forefront. Accurate and rapid bacterial identification results are highly beneficial to the diagnosis and therapeutic regime.

6.
World Allergy Organ J ; 17(5): 100905, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38742157

RESUMO

Background: Chronic Spontaneous Urticaria (CSU) is an immune-mediated skin disease that may require prolonged treatments. Currently, there are no recommendations for treatment discontinuation once CSU symptoms are controlled, particularly among patients primarily diagnosed with severe CSU. Objective: In this real-life study we aimed to describe our experience of omalizumab (Oma) treatment withdrawal in CSU and define biomarkers related to these outcomes. Methods: CSU patients followed at our allergy clinic from January 2016 to December 2022 were included. Response to Oma therapy, and Oma-withdrawal outcomes among patients who reached complete remission for >6 months were analyzed. Results: During the study period 192/335(%) CSU patients were categorized as severe-CSU and entitled to receive Oma according to our country's regulations. Of them, 131/192(68%) were considered "Oma-responders", and 95/131(72.5%) patients underwent gradual treatment withdrawal. Successful Oma-withdrawal was documented in 47/95(49.5%) whereas 48/95(50.5%) patients experienced flare and were defined as unsuccessful OMA-withdrawal. The first was associated with shorter disease duration 7.1 ± 7.4 years vs. 10.7 ± 9.4 (P = 0.042), lower baseline-IgE 81.6 ± 84.1IU/ml vs. 324.7 ± 555.9 (P = 0.005), and lower baseline-eosinophils count 131.4 ± 110.5 vs. 195.6 ± 98.4 (P = 0.043) in comparison to failure of Oma-withdrawal group. Conclusion: OMA may be successfully withdrawn in up to 50% of severe CSU patients following complete remission of disease symptoms, utilizing a gradual withdrawal protocol. Oma-withdrawal failure was linked with longer duration of disease as well as high IgE and eosinophil counts prior to initiation of Oma therapy. These parameters may enable the design of a treatment withdrawal algorithm.

7.
Cell Rep ; 43(5): 114197, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38733587

RESUMO

Interneurons (INs), specifically those in disinhibitory circuits like somatostatin (SST) and vasoactive intestinal peptide (VIP)-INs, are strongly modulated by the behavioral context. Yet, the mechanisms by which these INs are recruited during active states and whether their activity is consistent across sensory cortices remain unclear. We now report that in mice, locomotor activity strongly recruits SST-INs in the primary somatosensory (S1) but not the visual (V1) cortex. This diverse engagement of SST-INs cannot be explained by differences in VIP-IN function but is absent in the presence of visual input, suggesting the involvement of feedforward sensory pathways. Accordingly, inactivating the somatosensory thalamus, but not decreasing VIP-IN activity, significantly reduces the modulation of SST-INs by locomotion. Model simulations suggest that the differences in SST-INs across behavioral states can be explained by varying ratios of VIP- and thalamus-driven activity. By integrating feedforward activity with neuromodulation, SST-INs are anticipated to be crucial for adapting sensory processing to behavioral states.

8.
Neurosci Biobehav Rev ; 162: 105712, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38733896

RESUMO

Substance use disorders (SUDs) are severe psychiatric illnesses. Seed region and independent component analyses are currently the dominant connectivity measures but carry the risk of false negatives due to selection. They can be complemented by a data-driven and whole-brain usage of voxel-wise intrinsic measures (VIMs). We meta-analytically integrated VIMs, namely regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), voxel-mirrored homotopy connectivity (VMHC) and degree centrality (DC) across different SUDs using the Activation Likelihood Estimation (ALE) algorithm, functionally decoded emerging clusters, and analysed their connectivity profiles. Our systematic search identified 51 studies including 1439 SUD participants. Although no overall convergent pattern of alterations across VIMs in SUDs was found, sensitivity analyses demonstrated two ALE-derived clusters of increased ReHo and ALFF in SUDs, which peaked in the left pre- and postcentral cortices. Subsequent analyses showed their involvement in action execution, somesthesis, finger tapping and vibrotactile monitoring/discrimination. Their numerous clinical correlates across included studies highlight the under-discussed role of sensorimotor cortices in SUD, urging a more attentive exploration of their clinical significance.

9.
MethodsX ; 12: 102732, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38707213

RESUMO

The paper presents a comprehensive guide for researchers investigating mind-wandering and related phenomena such as involuntary past and future thinking. Examining such spontaneous cognitions presents a challenge requiring not only the use of appropriate laboratory-based procedures, but also the coding of complex qualitative data. This guide outlines two main stages of existing research protocols: data acquisition and data coding. For the former, we introduce an easily modifiable computerized version of the vigilance task, designed for broad application in studies focusing on eliciting and measuring involuntary thoughts in controlled laboratory conditions. Regarding data preparation and coding, we provide a detailed step-by-step procedure for categorizing and coding different types of thoughts, involving both participants and competent judges. Additionally, we address some of the difficulties that may arise during this categorization and coding process. The guide is supplemented by a clip demonstrating the main part of the experimental procedure and a step-by-step example of the subsequent data processing stages. We anticipate that this research guide will not only assist a broader group of researchers interested in investigating spontaneous cognition, but will also inspire future studies on spontaneous cognition and related phenomena.•There is a need for standardized approaches to working with qualitative data when investigating spontaneous thoughts.•The paper outlines a comprehensive protocol for collecting and coding involuntary past and future-oriented thoughts.•The paper also presents a detailed step-by-step procedure for data preparation and coding to categorize different types of thoughts, involving both participants and competent judges.

10.
Eur Heart J Case Rep ; 8(5): ytae204, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38707531

RESUMO

Background: One of the main causes of myocardial infarction during pregnancy is spontaneous coronary artery dissection. This is ascribed to hormonal changes during pregnancy leading to a weakening of the vessel wall and haemodynamic changes especially during childbirth. Management options include conservative medical treatment and percutaneous coronary intervention, depending on clinical presentation. Case summary: A 37-year-old woman presented with typical chest pain six weeks after giving birth to her third child. Echocardiography revealed a moderate reduction in systolic function. Initial invasive coronary angiography showed no abnormalities. After cardiac magnetic resonance demonstrated extensive scar, invasive coronary angiography was repeated including intravascular imaging. A dissection of the left anterior descending artery was visualized and treated by percutaneous coronary intervention and stenting. Left ventricular function was normalized at three-month follow-up. In this educational case report, we highlight the diagnostic and therapeutic challenges when treating this special patient cohort and the importance of cardiovascular imaging. Discussion: Pregnancy-associated spontaneous coronary dissection is a potential differential diagnosis when treating post-partum women with recent onset chest pain. Management is challenging and intravascular imaging to visualize dissection should be performed during invasive coronary angiography. Patients require interdisciplinary care within a pregnancy heart team.

11.
J Cell Physiol ; 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704705

RESUMO

Spontaneous abortion is the most common complication in early pregnancy, the exact etiology of most cases cannot be determined. Emerging studies suggest that mutations in ciliary genes may be associated with progression of pregnancy loss. However, the involvement of primary cilia on spontaneous abortion and the underlying molecular mechanisms remains poorly understood. We observed the number and length of primary cilia were significantly decreased in decidua of spontaneous abortion in human and lipopolysaccharide (LPS)-induced abortion mice model, accompanied with increased expression of proinflammatory cytokines interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α. The length of primary cilia in human endometrial stromal cell (hESC) was significantly shortened after TNF-α treatment. Knocking down intraflagellar transport 88 (IFT88), involved in cilia formation and maintenance, promoted the expression of TNF-α. There was a reverse regulatory relationship between cilia shortening and TNF-α expression. Further research found that shortened cilia impair decidualization in hESC through transforming growth factor (TGF)-ß/SMAD2/3 signaling. Primary cilia were impaired in decidua tissue of spontaneous abortion, which might be mainly caused by inflammatory injury. Primary cilia abnormalities resulted in dysregulation of TGF-ß/SMAD2/3 signaling transduction and decidualization impairment, which led to spontaneous abortion.

12.
Gynecol Endocrinol ; 40(1): 2351525, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38726683

RESUMO

OBJECTIVE: Stable luteal cell function is an important prerequisite for reproductive ability and embryonic development. However, luteal insufficiency seriously harms couples who have the desire to have a pregnancy, and the most important thing is that there is no complete solution. In addition, Vaspin has been shown to have regulatory effects on luteal cells, but the complex mechanisms involved have not been fully elucidated. Therefore, this study aimed to explore the effect of Vaspin on rat luteal cells and its mechanism. METHODS: Granulosa lutein cells separated from the ovary of female rats were incubated for 24h with gradient concentrations of Vaspin, and granulosa lutein cells incubated with 0.5% bovine serum albumin were used as controls. The proliferation, apoptosis, angiogenesis, progesterone (P4) and estradiol (E2) were detected by CCK-8, Anneixn-FITC/PI staining, angiogenesis experiment and ELISA. Western blot was applied to observe the expression levels of proteins related to cell proliferation, apoptosis, angiogenesis and MEK/MAPK signaling pathway. RESULTS: Compared with the Control group, Vaspin could significantly up-regulate the proliferation of granulosa lutein cells and reduce the apoptosis. Moreover, Vaspin promoted the angiogenesis of granulosa lutein cells and the production of P4 and E2 in a concentration-dependent manner. Furthermore, Vaspin up-regulated the CyclinD1, CyclinB1, Bcl2, VEGFA and FGF-2 expression in granulosa lutein cells, and down-regulated the level of Bax. Also, Vaspin increased the p-MEK1 and p-p38 levels. CONCLUSION: Vaspin can up-regulate the proliferation and steroidogenesis of rat luteal cells and reduce apoptosis, which may be related to the influence of MEK/MAPK activity.


Assuntos
Apoptose , Proliferação de Células , Células Lúteas , Progesterona , Serpinas , Animais , Feminino , Proliferação de Células/efeitos dos fármacos , Serpinas/metabolismo , Serpinas/farmacologia , Ratos , Células Lúteas/efeitos dos fármacos , Células Lúteas/metabolismo , Apoptose/efeitos dos fármacos , Progesterona/farmacologia , Estradiol/farmacologia , Células Cultivadas , Ratos Sprague-Dawley , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos
13.
Rozhl Chir ; 103(2): 65-67, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38697815

RESUMO

This case study presents a rare case of a 29-year-old woman with spontaneous pneumomediastinum who was treated in the emergency department for subjective dyspnea, rhinitis, and a subjectively reported increasing swelling of the throat. The clinical presentation was only characterized by crepitus in the neck and supraclavicular areas. CT scan of the neck and chest revealed massive emphysema of the soft tissues of the neck, chest, the right side of the face, and pneumomediastinum extending to the diaphragm. Based on the clinical presentation and imaging findings, which were consulted with thoracic surgeons, we assessed the condition as benign spontaneous pneumomediastinum. The patient was treated conservatively and discharged from the hospital on the third day of hospitalization with the need of aftercare.


Assuntos
Enfisema Mediastínico , Tomografia Computadorizada por Raios X , Humanos , Enfisema Mediastínico/diagnóstico por imagem , Feminino , Adulto , Síndrome
14.
Artigo em Inglês | MEDLINE | ID: mdl-38691287

RESUMO

Spontaneous combustion of coal gangue (CG) hills has caused varieties of secondary disasters that seriously endanger the ecological environment of the world. The emission law of index gases and their oxidation kinetics during the secondary oxidation process of CG with different ranks of oxidation were studied by using the temperature programmed device and online mass spectrometer (MS). Fourier transform infrared spectroscopy (FTIR) was used to reveal the changes of the CG internal active functional groups. The results showed that the energy required for the combustion of CG with low rank of pre-oxidation was significantly lower than that of the raw sample. However, as the oxidation rank increased, due to amounts of volatile components were released in the process of oxidation reaction, the CG in the combustion process of the emission of index gases and its oxygen consumption rate gradually reduced; the rapid oxidation stage shifted to the direction of the high temperature. In this study, the risk of spontaneous combustion of CG after oxidation at 80 â„ƒ under 3% oxygen concentration was the strongest. The results of this paper are of great guiding significance for exploring the spontaneous combustion characteristics of CG hills and their prevention by traditional covering method.

15.
Cereb Cortex ; 34(5)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38745558

RESUMO

Arousal state is regulated by subcortical neuromodulatory nuclei, such as locus coeruleus, which send wide-reaching projections to cortex. Whether higher-order cortical regions have the capacity to recruit neuromodulatory systems to aid cognition is unclear. Here, we hypothesized that select cortical regions activate the arousal system, which, in turn, modulates large-scale brain activity, creating a functional circuit predicting cognitive ability. We utilized the Human Connectome Project 7T functional magnetic resonance imaging dataset (n = 149), acquired at rest with simultaneous eye tracking, along with extensive cognitive assessment for each subject. First, we discovered select frontoparietal cortical regions that drive large-scale spontaneous brain activity specifically via engaging the arousal system. Second, we show that the functionality of the arousal circuit driven by bilateral posterior cingulate cortex (associated with the default mode network) predicts subjects' cognitive abilities. This suggests that a cortical region that is typically associated with self-referential processing supports cognition by regulating the arousal system.


Assuntos
Nível de Alerta , Encéfalo , Cognição , Conectoma , Imageamento por Ressonância Magnética , Descanso , Humanos , Nível de Alerta/fisiologia , Cognição/fisiologia , Masculino , Feminino , Conectoma/métodos , Adulto , Descanso/fisiologia , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Adulto Jovem , Rede Nervosa/fisiologia , Rede Nervosa/diagnóstico por imagem , Vias Neurais/fisiologia , Vias Neurais/diagnóstico por imagem
16.
Cureus ; 16(4): e58246, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38745793

RESUMO

A spontaneous rupture of the spleen during pregnancy or post-delivery is an exceptionally rare but potentially fatal maternal complication that poses a significant challenge in diagnosis and management. Herewith, we present a case of a 31-year-old female patient who experienced a spontaneous splenic rupture following a singleton vaginal delivery. Despite lacking any history of trauma or a predisposing factor, she developed symptoms of dizziness and postpartum abdominal pain, progressing rapidly to unconsciousness. Urgent abdominal ultrasound revealed significant intraperitoneal bleeding with a large peri-splenic hematoma, necessitating emergency exploratory laparotomy. Histopathological examination of a frozen section ruled out malignancy, and thus, a complete splenectomy was done, which confirmed the diagnosis of spontaneous splenic rupture. This case emphasizes the importance of close monitoring of all postpartum women, even those with low-risk pregnancies, for the early detection of any complication. Healthcare providers should maintain a high index of suspicion for rare but potentially life-threatening events to ensure timely intervention and optimal outcomes.

17.
Clin J Gastroenterol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748198

RESUMO

Spontaneous reactivation of the Hepatitis B virus (HBV) is rare in individuals with previously resolved infections. This report presents the case of a 71 year-old Japanese woman who experienced HBV reactivation without any prior immunosuppressive therapy or chemotherapy. Before the onset of liver injury, the patient was negative for hepatitis B surface antigen (HBsAg) but positive for hepatitis B surface antibody. She subsequently developed liver injury, with the reappearance of HBsAg and HBV DNA. The patient was successfully treated with tenofovir alafenamide, and prednisolone. Full-genome sequencing of HBV revealed subgenotype B1 without hepatitis B e-negative mutations in the precore and core promoter regions and 12 amino acid alterations in the pre-S1/S, P, and X genes. Notably, the S gene mutations D144A and K160N, which alter the antigenicity of HBsAg and potentially contribute to its reactivation, were identified. This case emphasizes the importance of vigilance for spontaneous reactivation of resolved HBV, highlighting the need for comprehensive genomic analysis to understand the associated virological intricacies.

18.
Proc Natl Acad Sci U S A ; 121(21): e2404763121, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38743626

RESUMO

Congenital stationary night blindness (CSNB) is an inherited retinal disease that causes a profound loss of rod sensitivity without severe retinal degeneration. One well-studied rhodopsin point mutant, G90D-Rho, is thought to cause CSNB because of its constitutive activity in darkness causing rod desensitization. However, the nature of this constitutive activity and its precise molecular source have not been resolved for almost 30 y. In this study, we made a knock-in (KI) mouse line with a very low expression of G90D-Rho (equal in amount to ~0.1% of normal rhodopsin, WT-Rho, in WT rods), with the remaining WT-Rho replaced by REY-Rho, a mutant with a very low efficiency of activating transducin due to a charge reversal of the highly conserved ERY motif to REY. We observed two kinds of constitutive noise: one being spontaneous isomerization (R*) of G90D-Rho at a molecular rate (R* s-1) 175-fold higher than WT-Rho and the other being G90D-Rho-generated dark continuous noise comprising low-amplitude unitary events occurring at a very high molecular rate equivalent in effect to ~40,000-fold of R* s-1 from WT-Rho. Neither noise type originated from G90D-Opsin because exogenous 11-cis-retinal had no effect. Extrapolating the above observations at low (0.1%) expression of G90D-Rho to normal disease exhibited by a KI mouse model with RhoG90D/WTand RhoG90D/G90D genotypes predicts the disease condition very well quantitatively. Overall, the continuous noise from G90D-Rho therefore predominates, constituting the major equivalent background light causing rod desensitization in CSNB.


Assuntos
Oftalmopatias Hereditárias , Doenças Genéticas Ligadas ao Cromossomo X , Miopia , Cegueira Noturna , Rodopsina , Animais , Cegueira Noturna/genética , Cegueira Noturna/metabolismo , Oftalmopatias Hereditárias/genética , Oftalmopatias Hereditárias/metabolismo , Camundongos , Rodopsina/genética , Rodopsina/metabolismo , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/metabolismo , Miopia/genética , Miopia/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/patologia , Escuridão , Transducina/genética , Transducina/metabolismo , Técnicas de Introdução de Genes , Modelos Animais de Doenças
19.
Exp Neurobiol ; 33(2): 68-76, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38724477

RESUMO

In the auditory system, the spontaneous activity of cochlear inner hair cells (IHCs) is initiated by the release of ATP from inner supporting cells (ISCs). This ATP release sets off a cascade, activating purinergic autoreceptors, opening of Ca2+-activated Cl- channel TMEM16A, Cl- efflux and osmotic cell shrinkage. Then, the shrunken ISCs efficiently regain their original volume, suggesting the existence of mechanisms for refilling Cland K+, priming them for subsequent activity. This study explores the potential involvement of NKCCs (Na+-K+-Cl- cotransporters) and KCCs (K+-Cl- cotransporters) in ISC spontaneous activity, considering their capability to transport both Cl- and K+ ions across the cell membrane. Employing a combination of immunohistochemistry, pharmacological interventions, and shRNA experiment, we unveiled the pivotal role of NKCC1 in cochlear spontaneous activity. Immunohistochemistry revealed robust NKCC1 expression in ISCs, persisting until the 2nd postnatal week. Intriguingly, we observed a developmental shift in NKCC1 expression from ISCs to synaptophysin-positive efferent terminals at postnatal day 18, hinting at its potential involvement in modulating synaptic transmission during the post-hearing period. Experiments using bumetanide, a well-known NKCC inhibitor, supported the functional significance of NKCC1 in ISC spontaneous activity. Bumetanide significantly reduced the frequency of spontaneous extracellular potentials (sEP) and spontaneous optical changes (sOCs) in ISCs. NKCC1-shRNA experiments conducted in cultured cochlear tissues further supported these findings, demonstrating a substantial decrease in event frequency and area. Taken together, we revealed the role of NKCC1 in shaping the ISC spontaneous activity that govern auditory pathway development.

20.
Transl Pediatr ; 13(4): 542-554, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38715667

RESUMO

Background: Spontaneous intestinal perforation (SIP) is one of the most serious surgical bowel conditions affecting preterm infants. There are limited data on the mortality and morbidities of very preterm infants [VPIs, <32 weeks' gestational age (GA)] with SIP in China. The study aimed to describe the prevalence, treatment, and outcomes of SIP among VPIs in China. Methods: This retrospective cohort study included all infants born at 24+0-31+6 weeks GA from January 1, 2019, to December 31, 2020, and admitted within seven days after birth to the neonatal intensive care units in the Chinese Neonatal Network. The primary outcome was survival without major morbidities. The association between SIP and neonatal outcomes was evaluated using multivariate logistic regression controlling for possible confounders. Results: Out of the 15,814 enrolled infants, 150 (1.0%) developed SIP with a median onset age of four (IQR 2-6) days. Infants with GA 24+0-25+6 weeks had the highest incidence of SIP (13/532, 2.4%), followed by those with GA 26+0-27+6 weeks (22/2,005, 1.1%), 28+0-29+6 weeks (44/5,269, 0.8%) and 30+0-31+6 weeks (71/8,008, 0.9%). Ten SIP cases were lost to follow-up with unknown survival status and 41 (29.3%) of the remaining 140 infants with SIP died during hospitalization. Only 29.3% of infants with SIP survived without major morbidities, significantly lower than those without SIP (59.2%; P<0.01). Multivariate analysis revealed SIP was associated with a higher risk of overall death (adjusted OR 3.36; 95% CI: 1.85 to 6.08), late-onset sepsis (adjusted OR 2.10; 95% CI: 1.02 to 4.31), and bronchopulmonary dysplasia (adjusted OR 2.49; 95% CI: 1.44 to 4.30). Among all infants with SIP, 28 (18.7%) did not receive any surgical intervention. Laparotomy was provided to 113 (92.6%) of the remaining 122 infants, solely (84/122, 68.9%) or following peritoneal drainage (29/122, 23.8%), while nine (7.4%) infants underwent peritoneal drainage only. Conclusions: Around 1% of VPIs in China developed SIP, associated with increased risk of mortality and morbidities. Over 90% of VPIs with SIP underwent laparotomy as initial or subsequent surgical treatment. Effective and evidence-based strategies are needed for the prevention and management of SIP.

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