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PloS One 2024Many newborn screening programs worldwide have introduced screening for diseases using DNA extracted from dried blood spots (DBS). In Germany, DNA-based assays are...
BACKGROUND
Many newborn screening programs worldwide have introduced screening for diseases using DNA extracted from dried blood spots (DBS). In Germany, DNA-based assays are currently used to screen for severe combined immunodeficiency (SCID), spinal muscular atrophy (SMA), and sickle cell disease (SCD).
METHODS
This study analysed the impact of pre-analytic DNA carry-over in sample preparation on the outcome of DNA-based newborn screening for SCID and SMA and compared the efficacy of rapid extraction versus automated protocols. Additionally, the distribution of T cell receptor excision circles (TREC) on DBS cards, commonly used for routine newborn screening, was determined.
RESULTS
Contaminations from the punching procedure were detected in the SCID and SMA assays in all experimental setups tested. However, a careful evaluation of a cut-off allowed for a clear separation of true positive polymerase chain reaction (PCR) amplifications. Our rapid in-house extraction protocol produced similar amounts compared to automated commercial systems. Therefore, it can be used for reliable DNA-based screening. Additionally, the amount of extracted DNA significantly differs depending on the location of punching within a DBS.
CONCLUSIONS
Newborn screening for SMA and SCID can be performed reliably. It is crucial to ensure that affected newborns are not overlooked. Therefore a carefully consideration of potential contaminating factors and the definition of appropriate cut-offs to minimise the risk of false results are of special concern. It is also important to note that the location of punching plays a pivotal role, and therefore an exact quantification of TREC numbers per μl may not be reliable and should therefore be avoided.
Topics: Humans; Neonatal Screening; Infant, Newborn; Muscular Atrophy, Spinal; Severe Combined Immunodeficiency; DNA; Dried Blood Spot Testing; High-Throughput Screening Assays; Polymerase Chain Reaction
PubMed: 38941330
DOI: 10.1371/journal.pone.0306329 -
The International Journal of Oral &... Jun 2024As the population gets older, the prevalence of complete or partial tooth loss is increasing, significantly impacting people's quality of life. Scientific research...
PURPOSE
As the population gets older, the prevalence of complete or partial tooth loss is increasing, significantly impacting people's quality of life. Scientific research demonstrates that implant-fixed complete dentures offer high levels of satisfaction. In certain cases, tooth loss can lead to significant bone atrophy, necessitating pre-implant bone reconstruction. We conducted a retrospective cohort study involving 43 arches, including or not bone grafts, rehabilitated using a stackable guided approach, which included an immediate loading protocol. The primary outcome measure was the survival rate of the implant at 4 months.
MATERIAL AND METHODS
The digital workflow helps the design of the provisional prothesis before the implant surgery, which will be loaded immediately after the implant's placement. The stacked guides integrate both surgical and prosthetic considerations into a digital workflow.
RESULT
A total of 284 implants were placed. After a 4-month follow-up period, 10 implants (3.5%) exhibited no osseointegration and were subsequently replaced, resulting in an overall success rate of 96.5%. After 1 year of follow-up, a prosthetic success rate of 100% was observed, with all patients being able to progress to the stages for the permanent fixed dentures.
CONCLUSION
Our findings support the use of this protocol for all patients, whether they require bone grafts or not. However, a long-term follow-up is essential for a comprehensive evaluation of these treatment outcomes.
PubMed: 38941165
DOI: 10.11607/jomi.10998 -
Clinical Microbiology Reviews Jun 2024SUMMARYThe gut microbiota is a major factor contributing to the regulation of energy homeostasis and has been linked to both excessive body weight and accumulation of... (Review)
Review
SUMMARYThe gut microbiota is a major factor contributing to the regulation of energy homeostasis and has been linked to both excessive body weight and accumulation of fat mass (i.e., overweight, obesity) or body weight loss, weakness, muscle atrophy, and fat depletion (i.e., cachexia). These syndromes are characterized by multiple metabolic dysfunctions including abnormal regulation of food reward and intake, energy storage, and low-grade inflammation. Given the increasing worldwide prevalence of obesity, cachexia, and associated metabolic disorders, novel therapeutic strategies are needed. Among the different mechanisms explaining how the gut microbiota is capable of influencing host metabolism and energy balance, numerous studies have investigated the complex interactions existing between nutrition, gut microbes, and their metabolites. In this review, we discuss how gut microbes and different microbiota-derived metabolites regulate host metabolism. We describe the role of the gut barrier function in the onset of inflammation in this context. We explore the importance of the gut-to-brain axis in the regulation of energy homeostasis and glucose metabolism but also the key role played by the liver. Finally, we present specific key examples of how using targeted approaches such as prebiotics and probiotics might affect specific metabolites, their signaling pathways, and their interactions with the host and reflect on the challenges to move from bench to bedside.
PubMed: 38940505
DOI: 10.1128/cmr.00045-23 -
Brain : a Journal of Neurology Jun 2024In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional...
In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degeneration patterns relate to regional gene expression of human accelerated regions (HARs), conserved sequences that have undergone positive selection during recent human evolution. To this end, we used structural neuroimaging from patients with FTLD and human brain regional transcriptomic data from controls to identify genes expressed in FTLD-targeted brain regions. We then integrated primate comparative genomic data to test our hypothesis that FTLD targets brain regions linked to expression levels of recently evolved genes. In addition, we asked whether genes whose expression correlates with FTLD atrophy are enriched for genes that undergo cryptic splicing when TDP-43 function is impaired. We found that FTLD-TDP and FTLD-tau subtypes target brain regions with overlapping and distinct gene expression correlates, highlighting many genes linked to neuromodulatory functions. FTLD atrophy-correlated genes were strongly enriched for HARs. Atrophy-correlated genes in FTLD-TDP showed greater overlap with TDP-43 cryptic splicing genes and genes with more numerous TDP-43 binding sites compared with atrophy-correlated genes in FTLD-tau. Cryptic splicing genes were enriched for HAR genes, and vice versa, but this effect was due to the confounding influence of gene length. Analyses performed at the individual-patient level revealed that the expression of HAR genes and cryptically spliced genes within putative regions of disease onset differed across FTLD-TDP subtypes.
PubMed: 38940350
DOI: 10.1093/brain/awae205 -
The Journal of Dermatology Jun 2024Vulvar lichen sclerosus (VLS) is a chronic, inflammatory disease which is accompanied by itching and pain, affecting the patient's daily life and sexual activity....
Vulvar lichen sclerosus (VLS) is a chronic, inflammatory disease which is accompanied by itching and pain, affecting the patient's daily life and sexual activity. However, the disease characteristics of children and adults are not completely the same. Currently, there are few studies in China that compare the characteristics of VLS between girls and adult female patients. The aim of this study was to compare the epidemiology, clinical features, and combined autoimmune diseases of VLS patients between girls and adult females, and to help clinicians better understand VLS in different age groups. We enrolled 744 female patients for analysis, divided by age into a child group (<18 years) and an adult group (≥18 years). Among girl patients, 94.6% had preadolescent onset, while among adult female patients, only 4.6% had preadolescent onset, which was a statistically significant difference. The highest percentage of adult female patients had onset during their child-bearing period (75.4%), while 20% had postmenopausal onset, with a significant difference when the three onset states were compared. White patches were equally common in both girl and adult female patients' external genital area, while mossy lesions and labia minora atrophy were more common in adult female patients. Involvement of the clitoris, labia minora, and vaginal opening area were more common in adult patients. The perianal area was more commonly involved in girl patients. We found eight cases (1.2%) of secondary squamous cell carcinoma in adult female patients. We also found that 13 patients had concurrent lichen sclerosus lesions on the vulva and extragenital region, including two girls and 11 adult females. Extragenital lichen sclerosus (EGLS) occurred mostly in the torso. Clinicians should be aware of these differences so that early diagnosis and treatment of the disease can be achieved, to avoid irreversible anatomical alterations and the risk of cancer.
PubMed: 38940217
DOI: 10.1111/1346-8138.17352 -
Expert Opinion on Biological Therapy Jun 2024Leber hereditary optic neuropathy (LHON) is among the most frequent inherited mitochondrial disease, causing a severe visual impairment, mostly in young-adult males. The... (Review)
Review
INTRODUCTION
Leber hereditary optic neuropathy (LHON) is among the most frequent inherited mitochondrial disease, causing a severe visual impairment, mostly in young-adult males. The causative mtDNA variants (the three common are m.11778 G>A/MT-ND4, m.3460 G>A/MT-ND1, and m.14484T>C/MT-ND6) by affecting complex I impair oxidative phosphorylation in retinal ganglion cells, ultimately leading to irreversible cell death and consequent functional loss. The gene therapy based on allotopic expression of a wild-type transgene carried by adeno-associated viral vectors (AVV-based) appears a promising approach in mitochondrial disease and its efficacy has been explored in several large clinical trials.
AREAS COVERED
The review work employed basic concepts in mitochondrial diseases, LHON, and gene therapy procedures. Reports from completed trials in LHON (i.e. RESCUE) were reviewed and critically compared.
EXPERT OPINION
New challenges, as the improvement of the contralateral untreated eye or the apparently better outcome in patients treated in later stages (6-12 months), were highlighted by the latest gene therapy trials. A better understanding of the pathogenetic mechanisms of the disease together with combined therapy (medical and gene therapy) and optimization in genetic correction approaches could improve the visual outcome of treated eyes.
Topics: Optic Atrophy, Hereditary, Leber; Humans; Genetic Therapy; DNA, Mitochondrial; Animals; Dependovirus; Genetic Vectors
PubMed: 38939999
DOI: 10.1080/14712598.2024.2359015 -
Journal of Extracellular Biology Nov 2023Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy body (DLB), corticobasal syndrome (CBS) and progressive... (Review)
Review
Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy body (DLB), corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP) are often misdiagnosed due to overlapping symptoms and the absence of precise biomarkers. Furthermore, there are no current methods to ascertain the progression and conversion of prodromal conditions such as REM behaviour disorder (RBD). Extracellular vesicles (EVs), containing a mixture of biomolecules, have emerged as potential sources for parkinsonian diagnostics. However, inconsistencies in previous studies have left their diagnostic potential unclear. We conducted a meta-analysis, following PRISMA guidelines, to assess the diagnostic accuracy of general EVs isolated from various bodily fluids, including cerebrospinal fluid (CSF), plasma, serum, urine or saliva, in differentiating patients with parkinsonian disorders from healthy controls (HCs). The meta-analysis included 21 studies encompassing 1285 patients with PD, 24 with MSA, 105 with DLB, 99 with PSP, 101 with RBD and 783 HCs. Further analyses were conducted only for patients with PD versus HCs, given the limited number for other comparisons. Using bivariate and hierarchal receiver operating characteristics (HSROC) models, the meta-analysis revealed moderate diagnostic accuracy in distinguishing patients with PD from HCs, with substantial heterogeneity and publication bias. The trim-and-fill method revealed at least two missing studies with null or low diagnostic accuracy. CSF-EVs showed better overall diagnostic accuracy, while plasma-EVs had the lowest performance. General EVs demonstrated higher diagnostic accuracy compared to CNS-originating EVs, which are more time-consuming, labour- and cost-intensive to isolate. In conclusion, while holding promise, utilizing biomarkers in general EVs for PD diagnosis remains unfeasible due to existing challenges. The focus should shift toward harmonizing the field through standardization, collaboration, and rigorous validation. Current efforts by the International Society For Extracellular Vesicles (ISEV) aim to enhance the accuracy and reproducibility of EV-related research through rigor and standardization, aiming to bridge the gap between theory and practical clinical application.
PubMed: 38939363
DOI: 10.1002/jex2.121 -
Frontiers in Surgery 2024Cervical spondylotic amyotrophy (CSA) is a special type of cervical spondylosis based on cervical degeneration, which is mainly manifested by weakness and atrophy of...
BACKGROUND
Cervical spondylotic amyotrophy (CSA) is a special type of cervical spondylosis based on cervical degeneration, which is mainly manifested by weakness and atrophy of upper limb muscles without obvious sensory impairment. Various diagnostic and treatment strategies used; however, discrepancies exist. We tried to discuss diagnosing and treating CSA.
METHODS
15 patients with CSA were diagnosed in the Orthopedics Department of the First Affiliated Hospital of Zhengzhou University, aged 42-70 years old. The duration of preoperative symptoms of amyotrophy was 6 to 240 months. 12 patients received surgical treatment, and 3 patients received conservative treatment. The patients were divided into two groups according to the site of preoperative amyotrophy. The manual muscle test was used to evaluate the patients' muscle strength pre-and postoperatively.
RESULTS
During postoperative follow-up, the muscle strength of 12 patients improved to different degrees compared to before surgery. The improvement effect was excellent in 2 cases, good in 6, and moderate in 4. There was no decrease in postoperative muscle strength compared with that before surgery. The satisfaction rate of the effect was 66.7%. The two groups had no statistically significant difference in preoperative muscle strength. The postoperative muscle strength of the proximal group was significantly better than that of the distal group.
CONCLUSION
The surgical effect of CSA of the proximal type is significantly better than that of the distal type. The recovery effect of amyotrophy after surgery for distal type CSA is poor; thus, surgical treatment should be carefully considered.
PubMed: 38939077
DOI: 10.3389/fsurg.2024.1409283 -
Frontiers in Neurology 2024Peripheral nerve injuries (PNI) represent one of the primary neuropathies leading to lifelong disability. Nerve regeneration and targeted muscle atrophy stand as the two... (Review)
Review
Peripheral nerve injuries (PNI) represent one of the primary neuropathies leading to lifelong disability. Nerve regeneration and targeted muscle atrophy stand as the two most crucial factors influencing functional rehabilitation post peripheral nerve injury. Over time, traditional Chinese medicine (TCM) rehabilitation approaches such as acupuncture, Tuina, and microneedles serve as pivot means to activate the regeneration of injured nerve Schwann cells. By promoting axon regeneration, these approaches can accomplish nerve repair, reconstruction, and functional rehabilitation. Although TCM rehabilitation approaches have clinically demonstrated effectiveness in promoting the repair and regeneration of PNI, the related molecular mechanisms remain unclear. This significantly hampers the application and promotion of TCM rehabilitation in PNI recovery. Therefore, deeply delving into the cellular and molecular mechanisms of TCM rehabilitation technologies to foster nerve regeneration stands as the most pressing issue. On the other hand, in recent years, novel biomaterials represented by hydrogels, microfluidic platforms, and new chitosan scaffolds have showed their unique roles in treating various degrees of nerve injury. These methods exhibit immense potential in conducting high-throughput cell and organoid culture and synthesizing diverse tissue engineering scaffolds and drug carriers. We believe that the combination of TCM rehabilitation technology and novel biomaterials can more effectively address precise treatment issues such as identification of treatment target and dosage control. Therefore, this paper not only summarizes the molecular mechanisms of TCM rehabilitation technology and novel biomaterials in treating peripheral nerve injury individually, but also explores the research direction of precise treatment by integrating the two at both macro and micro levels. Such integration may facilitate the exploration of cellular and molecular mechanisms related to neurodegeneration and regeneration, providing a scientific and theoretical foundation for the precise functional rehabilitation of PNI in the future.
PubMed: 38938781
DOI: 10.3389/fneur.2024.1421772 -
Frontiers in Neurology 2024Real-world studies have shown the sustained therapeutic effect and favourable safety profile of OnabotulinumtoxinA (BoNTA) in the long term and up to 4 years of...
BACKGROUND
Real-world studies have shown the sustained therapeutic effect and favourable safety profile of OnabotulinumtoxinA (BoNTA) in the long term and up to 4 years of treatment in chronic migraine (CM). This study aims to assess the safety profile and efficacy of BoNTA in CM after 5 years of treatment in a real-life setting.
METHODS
We performed a retrospective chart review of patients with CM in relation to BoNTA treatment for more than 5 years in 19 Spanish headache clinics. We excluded patients who discontinued treatment due to lack of efficacy or poor tolerability.
RESULTS
489 patients were included [mean age 49, 82.8% women]. The mean age of onset of migraine was 21.8 years; patients had CM with a mean of 6.4 years (20.8% fulfilled the aura criteria). At baseline, patients reported a mean of 24.7 monthly headache days (MHDs) and 15.7 monthly migraine days (MMDs). In relation to effectiveness, the responder rate was 59.1% and the mean reduction in MMDs was 9.4 days (15.7 to 6.3 days; < 0.001). The MHDs were also reduced by 14.9 days (24.7 to 9.8 days; < 0.001). Regarding the side effects, 17.5% experienced neck pain, 17.3% headache, 8.5% eyelid ptosis, 7.5% temporal muscle atrophy and 3.2% trapezius muscle atrophy. Furthermore, after longer-term exposure exceeding 5 years, there were no serious adverse events (AE) or treatment discontinuation because of safety or tolerability issues.
CONCLUSION
Treatment with BoNTA led to sustained reductions in migraine frequency, even after long-term exposure exceeding 5 years, with no evidence of new safety concerns.
PubMed: 38938776
DOI: 10.3389/fneur.2024.1417831