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Medicine Jun 2024Disorders of sex development (DSD) are congenital conditions characterized by atypical development of chromosomal, gonadal, and phenotypic sex. 46, XY DSD can result...
BACKGROUND
Disorders of sex development (DSD) are congenital conditions characterized by atypical development of chromosomal, gonadal, and phenotypic sex. 46, XY DSD can result from disorders of testicular development or androgen synthesis.
METHODS
We present 2 rare cases of 46, XY DSD, specifically XY pure gonadal dysgenesis and complete androgen insensitivity syndrome.
RESULTS
Both cases underwent prophylactic gonadectomy due to the elevated risk of gonadal malignancy. Bilateral gonadoblastoma and dysgerminoma were diagnosed on one side, while Leydig cell hyperplasia and only Sertoli cells were diagnosed in the seminiferous tubules on both sides. The normal menstruation for the pure gonadal dysgenesis patient only as CAIS patients never menstruate. Estrogen replacement therapy was administered periodically to promote the development of secondary sexual characteristics and menstruation in pure gonadal dysgenesis case, as well as to prevent osteoporosis. Follow-up examinations revealed no tumor recurrence, and the patient with Swyer syndrome had regular menstrual cycles.
CONCLUSION
Laparoscopic bilateral prophylactic gonadectomy and long-term hormone therapy with patient counseling and support are recommended.
Topics: Humans; Androgen-Insensitivity Syndrome; Male; Gonadal Dysgenesis, 46,XY; Female; Gonadoblastoma
PubMed: 38905377
DOI: 10.1097/MD.0000000000038297 -
Frontiers in Pediatrics 2024West syndrome (WS) is a devastating epileptic encephalopathy with onset in infancy and early childhood. It is characterized by clustered epileptic spasms, developmental...
BACKGROUND
West syndrome (WS) is a devastating epileptic encephalopathy with onset in infancy and early childhood. It is characterized by clustered epileptic spasms, developmental arrest, and interictal hypsarrhythmia on electroencephalogram (EEG). Hypsarrhythmia is considered the hallmark of WS, but its visual assessment is challenging due to its wide variability and lack of a quantifiable definition. This study aims to analyze the EEG patterns in WS and identify computational diagnostic biomarkers of the disease.
METHOD
Linear and non-linear features derived from EEG recordings of 31 WS patients and 20 age-matched controls were compared. Subsequently, the correlation of the identified features with structural and genetic abnormalities was investigated.
RESULTS
WS patients showed significantly elevated alpha-band activity (0.2516 vs. 0.1914, < 0.001) and decreased delta-band activity (0.5117 vs. 0.5479, < 0.001), particularly in the occipital region, as well as globally strengthened theta-band activity (0.2145 vs. 0.1655, < 0.001) in power spectrum analysis. Moreover, wavelet-bicoherence analysis revealed significantly attenuated cross-frequency coupling in WS patients. Additionally, bi-channel coherence analysis indicated minor connectivity alterations in WS patients. Among the four non-linear characteristics of the EEG data (i.e., approximate entropy, sample entropy, permutation entropy, and wavelet entropy), permutation entropy showed the most prominent global reduction in the EEG of WS patients compared to controls (1.4411 vs. 1.5544, < 0.001). Multivariate regression results suggested that genetic etiologies could influence the EEG profiles of WS, whereas structural factors could not.
SIGNIFICANCE
A combined global strengthening of theta activity and global reduction of permutation entropy can serve as computational EEG biomarkers for WS. Implementing these biomarkers in clinical practice may expedite diagnosis and treatment in WS, thereby improving long-term outcomes.
PubMed: 38903771
DOI: 10.3389/fped.2024.1406772 -
Frontiers in Genetics 2024In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England, requiring the coordination of care from...
INTRODUCTION
In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England, requiring the coordination of care from specialist genetics, fetal medicine (FM) and laboratory services. This mixed methods study explored the experiences of professionals involved in delivering the pES service during the first 2 years of its delivery in the NHS.
METHODS
A survey ( = 159) and semi-structured interviews ( = 63) with healthcare professionals, including clinical geneticists, FM specialists, and clinical scientists (interviews only) were used to address: 1) Views on the pES service; 2) Capacity and resources involved in offering pES; 3) Awareness, knowledge, and educational needs; and 4) Ambitions and goals for the future.
RESULTS
Overall, professionals were positive about the pES service with 77% rating it as Good or Excellent. A number of benefits were reported, including the increased opportunity for receiving actionable results for parental decision-making, improving equity of access to genomic tests and fostering close relationships between FM and genetics departments. Nonetheless, there was evidence that the shift to offering pES in a clinical setting had brought some challenges, such as additional clinic time, administrative processes, perceived lack of autonomy in decision-making regarding pES eligibility and difficulty engaging with peripheral maternity units. Concerns were also raised about the lack of confidence and gaps in genomics knowledge amongst non-genetics professionals - especially midwives. However, the findings also highlighted value in both FM, obstetric and genetics professionals benefiting from further training with a focus on recognising and managing prenatally diagnosed genetic conditions.
CONCLUSION
Healthcare professionals are enthusiastic about the benefits of pES, and through multi-collaborative working, have developed relationships that have contributed to effective communication across specialisms. Although limitations on resources and variation in knowledge about pES have impacted service delivery, professionals were hopeful that improvements to infrastructure and the upskilling of all professionals involved in the pathway would optimise the benefits of pES for both parents and professionals.
PubMed: 38903755
DOI: 10.3389/fgene.2024.1401705 -
Indian Journal of Anaesthesia Jun 2024
PubMed: 38903250
DOI: 10.4103/ija.ija_5_24 -
Journal of Neurochemistry Jun 2024Kelch-like family member 17 (KLHL17), an actin-associated adaptor protein, is linked to neurological disorders, including infantile spasms and autism spectrum disorders....
Kelch-like family member 17 (KLHL17), an actin-associated adaptor protein, is linked to neurological disorders, including infantile spasms and autism spectrum disorders. The key morphological feature of Klhl17-deficient neurons is impaired dendritic spine enlargement, resulting in the amplitude of calcium events being increased. Our previous studies have indicated an involvement of F-actin and the spine apparatus in KLHL17-mediated dendritic spine enlargement. Here, we show that KLHL17 further employs different mechanisms to control the expression of two types of glutamate receptors, that is, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and kainate receptors (KARs), to regulate dendritic spine enlargement and calcium influx. We deployed proteomics to reveal that KLHL17 interacts with N-ethylmaleimide-sensitive fusion protein (NSF) in neurons, with this interaction of KLHL17 and NSF enhancing NSF protein levels. Consistent with the function of NSF in regulating the surface expression of AMPAR, Klhl17 deficiency limits the surface expression of AMPAR, but not its total protein levels. The NSF pathway also contributes to synaptic F-actin distribution and the dendritic spine enlargement mediated by KLHL17. KLHL17 is known to act as an adaptor mediating degradation of the KAR subunit GluK2 by the CUL3 ubiquitin ligase complex, and Klhl17 deficiency impairs activity-dependent degradation of GluK2. Herein, we further demonstrate that GluK2 is critical to the increased amplitude of calcium influx in Klhl17-deficient neurons. Moreover, GluK2 is also involved in KLHL17-regulated dendritic spine enlargement. Thus, our study reveals that KLHL17 controls AMPAR and KAR expression via at least two mechanisms, consequently regulating dendritic spine enlargement. The regulatory effects of KLHL17 on these two glutamate receptors likely contribute to neuronal features in patients suffering from certain neurological disorders.
PubMed: 38898681
DOI: 10.1111/jnc.16148 -
The Neurohospitalist Jul 2024Dengue neuro-infection can present with symptoms ranging from mild to severe. Atypical presentations, such as expanded dengue syndrome, pose diagnostic and therapeutic...
BACKGROUND
Dengue neuro-infection can present with symptoms ranging from mild to severe. Atypical presentations, such as expanded dengue syndrome, pose diagnostic and therapeutic challenges. Neuroimaging findings, particularly the "double-doughnut" sign on brain magnetic resonance imaging (MRI), have emerged as one of the most valuable aids in diagnosing complex cases of central nervous system infection by dengue virus.
CASE PRESENTATION
We report the case of a 35-year-old female from rural West Bengal, India, with expanded dengue syndrome. The patient presented with fever, headaches, body aches, and sudden disorientation over minutes, which progressed to a coma. Neurological examination revealed profound unconsciousness and nuchal rigidity. Laboratory findings were consistent with dengue infection, including altered liver and pancreatic enzyme levels. The diagnosis was facilitated by identifying the "double-doughnut" sign on the brain MRI, which suggested dengue encephalitis. This finding and clinical and serological evidence guided the treatment strategy.
DISCUSSION
The "double-doughnut" sign, though not exclusive to dengue encephalitis, proved crucial in this case, aiding in differentiating from other causes of encephalitis. Recognition of this sign can be pivotal in diagnosing expanded dengue syndrome, facilitating timely and appropriate intervention, and improving patient outcomes. This case also underscores the importance of considering dengue in the differential diagnosis of encephalitis, especially in endemic areas. Also, this case's excellent outcome (both clinically and radiologically) was noteworthy.
PubMed: 38894998
DOI: 10.1177/19418744241230730 -
Movement Disorders : Official Journal... Jun 2024
PubMed: 38894500
DOI: 10.1002/mds.29868 -
Cancers May 2024Sézary syndrome (SS) is a rare primary cutaneous T-cell lymphoma variant. Despite various treatment options, it remains incurable, with a poor prognosis. There is an...
Sézary syndrome (SS) is a rare primary cutaneous T-cell lymphoma variant. Despite various treatment options, it remains incurable, with a poor prognosis. There is an urgent need for additional descriptive research to enhance our understanding and treatment of SS. The aim of this retrospective register-based study was to outline patients' demographic characteristics; investigate the clinical, histopathological, and molecular findings; and assess treatment effectiveness with a focus on time to next treatment (TTNT) and disease progression. Data on 17 patients with SS were obtained from the primary cutaneous lymphoma register in West Sweden between 2012 and 2024. The results revealed that not all patients exhibited the classical triad of symptoms at diagnosis, emphasizing the need for personalized diagnostic approaches. The median survival was only 2.1 years, which reflects the aggressive nature of SS. The longest median TTNT was observed in triple therapy involving retinoids, interferon alpha, and extracorporeal photopheresis (ECP). There was no significant difference in TTNT between various lines of treatment. Early initiation of ECP treatment did not result in improved outcomes. This study highlights the importance of combination therapy for improved outcomes and underscores the need for future studies to identify optimal treatment approaches.
PubMed: 38893069
DOI: 10.3390/cancers16111948 -
Healthcare (Basel, Switzerland) May 2024Non-alcoholic fatty liver disease (NAFLD) is common and presents in a large proportion-up to 30%-of the global adult female population. Several factors have been linked... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is common and presents in a large proportion-up to 30%-of the global adult female population. Several factors have been linked with NAFLD in women, such as age, obesity, and metabolic syndrome. To extract appropriate details about the topic, we conducted an extensive search using various medical subject headings and entry terms including 'Menopause', 'Non-alcoholic fatty liver disease', 'Insulin resistance', and 'BMI'. This exhaustive search resulted in a total of 180 studies, among which only 19 were able to meet the inclusion criteria. While most of these studies indicated a significant rise in NAFLD prevalence among postmenopausal women, two did not find strong evidence linking menopause with NAFLD. Moreover, it was observed that women with NAFLD had higher insulin resistance levels and BMIs compared to those without the condition. In summary, it is important to consider specific factors like risk profile, hormonal status, and age along with metabolic components when treating women presenting with NAFLD. There is need for data-driven research on how gender affects the sensitivity of biomarkers towards NAFLD as well as the development of sex-specific prediction models-this would help personalize management approaches for women, who stand to benefit greatly from such tailored interventions.
PubMed: 38891156
DOI: 10.3390/healthcare12111081 -
Foods (Basel, Switzerland) Jun 2024Metabolic syndrome (MetS) significantly predisposes individuals to diabetes and is a prognostic factor for the progression of diabetic nephropathy (DN). This study aimed...
Metabolic syndrome (MetS) significantly predisposes individuals to diabetes and is a prognostic factor for the progression of diabetic nephropathy (DN). This study aimed to evaluate the efficacy of (-)-gallocatechin gallate (GCG) in alleviating signs of MetS-associated DN in mice. We administered GCG and monitored its effects on several metabolic parameters, including food and water intake, urinary output, blood glucose levels, glucose and insulin homeostasis, lipid profiles, blood pressure, and renal function biomarkers. The main findings indicated that GCG intervention led to marked improvements in these metabolic indicators and renal function, signifying its potential in managing MetS and DN. Furthermore, transcriptome analysis revealed substantial modifications in gene expression, notably the downregulation of pro-inflammatory genes such as , , , , , , , -, , , and and the upregulation of the anti-oxidative gene . These genetic alterations suggest significant effects on pathways related to inflammation and oxidative stress. In conclusion, GCG demonstrates therapeutic efficacy for MetS-associated DN, mitigating metabolic disturbances and enhancing renal health by modulating inflammatory and oxidative responses.
PubMed: 38890983
DOI: 10.3390/foods13111755