Red cabbage (RC) represents a source of anthocyanins acylated with hydroxycinnamic acids (HCA) that are described to enhance their stability. Nevertheless, data about their thermal degradation are ...still controversial. Our aim was to comprehensively analyse the degradation kinetics of individual RC anthocyanins in a model aqueous extract treated at 40 °C × 30 days to simulate severe but realistic storage conditions. Free anthocyanins and radical-scavenging capacity showed different kinetics. The results confirm the high stability of RC anthocyanins (t
: 16.4-18.4 days), although HPLC analyses of each molecule displayed distinct kinetics with t
from 12.6 to 35.1 days. In particular, the sinapoyl acylation negatively affected the stability of the anthocyanins, while the forms monoacylated with glycosyl p-coumaric and ferulic acids exhibited higher stability. In conclusion, our results indicate that acylation is not a prerogative of stability, as this is instead more dependent on specific acylation patterns and the glycosylation of HCA.
To describe the patterns of health care utilization among patients with chronic pelvic pain.
Deidentified administrative claims data from the OptumLabs Data Warehouse were used. Adult female patients ...who had their first medical claim for chronic pelvic pain between January 1, 2016, and December 31, 2019, were included. Utilization was examined for 12 months after the index diagnosis. The greedy nearest neighbor matching method was used to identify a control group of individuals without chronic pelvic pain. Comparisons were made between those with and those without chronic pelvic pain using χ2 tests for categorical data and Wilcoxon rank-sum tests for continuous data.
In total, 18,400 patients were analyzed in the chronic pelvic pain cohort. Patients with chronic pelvic pain had a higher rate of chronic overlapping pain conditions. Patients with chronic pelvic pain had higher rates of health care utilization across all queried indices. They had more outpatient office visits; 55.5% had 10 or more office visits. Patients with chronic pelvic pain showed higher utilization of the emergency department (ED) (6.3 visits vs 1.9 visits; P<.001). Urine culture and pelvic ultrasonography were the most utilized tests. One-third of patients with chronic pelvic pain utilized physical therapy (PT), and 13% utilized psychological or behavioral therapy. Patients with chronic pelvic pain had higher rates of hysterectomy (8.9% vs 0.6%). The average total health care costs per patient with chronic pelvic pain per year was $12,254.
Patients with chronic pelvic pain have higher rates of chronic overlapping pain conditions and undergo more ED visits, imaging tests, and hysterectomies than patients without chronic pelvic pain. Improving access to multidisciplinary care, increasing utilization of interventions such as PT and psychological or behavioral therapy, and reducing ED utilization may be possible targets to help reduce overall health care costs and improve patient care.
Background Pompe disease, a rare autosomal recessive disorder caused by acid alpha-glucosidase deficiency, results in progressive glycogen accumulation and multisystem dysfunction. Enzyme replacement ...therapy with recombinant human acid alpha-glucosidase is the standard of care; however, some patients develop anti-recombinant human acid alpha-glucosidase antibodies, leading to reduced efficacy. This case report presents two infants with early-onset Pompe disease who developed IgG antibodies to enzyme replacement therapy and were subsequently treated with methotrexate, highlighting the importance of monitoring antibody development and exploring alternative therapeutic approaches. Case presentation Patient 1, a 10-month-old female from Bogota, Colombia, presented with generalized hypotonia, macroglossia, hyporeflexia, and mild left ventricular hypertrophy. Diagnostic tests confirmed early-onset Pompe disease, and enzyme replacement therapy was started at 12 months. Due to a lack of improvement and high anti-recombinant human acid alpha-glucosidase IgG antibody titers (1:1800), methotrexate was started at 18 months. After 8 months of combined therapy, antibody titers were negative and significant improvement in motor function was observed using the Gross Motor Function Measure 88. Patient 2, a 7-year-old female from Bogota, Colombia, was diagnosed with early-onset Pompe disease at 12 months and initiated enzyme replacement therapy. At 5 years of age, she experienced frequent falls and grip strength alterations. Functional tests revealed motor development delay, generalized hypotonia, and positive anti-recombinant human acid alpha-glucosidase IgG antibody titers (6400). Methotrexate was initiated, leading to a reduction in falls and antibody titers (3200) after 6 months, with no adverse events or complications. Motor function improvement was assessed using the Motor Function Measurement 32. Conclusions The presented cases highlight the importance of monitoring patients for anti-recombinant human acid alpha-glucosidase antibody development during enzyme replacement therapy and the potential benefit of methotrexate as an immunomodulatory agent in early-onset Pompe disease. Early diagnosis and timely initiation of enzyme replacement therapy, combined with prophylactic immune tolerance induction, may improve clinical outcomes and reduce the development of anti-recombinant human acid alpha-glucosidase antibodies. The cases also highlight the importance of objective motor function assessment tools, such as Gross Motor Function Measure 88 and Motor Function Measurement 32, in assessing treatment response. Further research is needed to optimize treatment regimens, monitor long-term effects, and address the current limitations of enzyme replacement therapy in Pompe disease. Keywords: Pompe disease, Enzyme replacement therapy (ERT), Acid alpha-glucosidase (GAA), Lysosomal storage disorders
Endometriosis biomarkers of the disease: an update Encalada Soto, Diana; Rassier, Sarah; Green, Isabel C ...
Current opinion in obstetrics & gynecology,
08/2022, Letnik:
34, Številka:
4
Journal Article
Recenzirano
Endometriosis is a complex benign gynaecologic condition with heterogenous presentations and a large impact on the global healthcare system and on the quality of life for millions of women. ...Currently, the gold standard for diagnosis involves direct visualization of lesions during surgery confirmed by histopathological diagnosis, resulting in an average delay in its initial diagnosis of 8-10 years. Therefore, the search for noninvasive diagnostic testing options has been subject to a large body of research.
Multiple potential biomarkers have been explored for noninvasive testing for endometriosis, including glycoproteins, inflammatory cytokines, immunological molecules, angiogenesis markers, hormones, micro RNAs (miRNAs), proteomics, metabolomics, genomics and the microbiome.
Although there are challenges to consider, areas for real promise and advancement in the noninvasive diagnosis of endometriosis are currently being explored with real promise in the area of miRNAs, proteomics, metabolomics, genomics and the microbiome.
The Mexican population is characterized by high and particular admixture, and the picture of variants associated with disease remains unclear. Here we investigated the distribution of single ...nucleotide polymorphisms (SNPs) in the Mexican population. We focused on two non-synonymous and three synonymous SNPs in the beta-2 adrenergic receptor gene (ADRB2), which plays key roles in energy balance regulation. These SNPs were genotyped in 2,011 Mexican Amerindians (MAs) belonging to 62 ethnic groups and in 1,980 geographically matched Mexican Mestizos (MEZs). The frequency distribution of all five ADRB2 variants significantly differed between MAs, MEZs, and other continental populations (CPs) from the 1000 Genomes database. Allele frequencies of the three synonymous SNPs rs1042717A, rs1042718A, and rs1042719C were significantly higher in Mexican individuals, particularly among MAs, compared to in the other analyzed populations (P<0.05). The non-synonymous ADRB2 Glu27 allele (rs1042714G), which is associated with several common conditions, showed the lowest frequency in MAs (0.03) compared to other populations worldwide. Among MEZs, this allele showed a frequency of 0.15, intermediate between that in MAs and in Iberians (0.43). Moreover, Glu27 was the only SNP exhibiting a geographic gradient within the MEZ population (from 0.22 to 0.11), reflecting admixed mestizo ancestry across the country. Population differentiation analysis demonstrated that Glu27 had the highest FST value in MAs compared with Europeans (CEU) (0.71), and the lowest between MAs and Japanese (JPT) (0.01), even lower than that observed between MAs and MEZs (0.08). This analysis demonstrated the genetic diversity among Amerindian ethnicities, with the most extreme FST value (0.34) found between the Nahuatls from Morelos and the Seris. This is the first study of ADRB2 genetic variants among MA ethnicities. Our findings add to our understanding of the genetic contribution to variability in disease susceptibility in admixed populations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•The ABC classification problem is solved using a discrete artificial neural network.•A randomized greedy multi-start algorithm is designed to train the neural network.•The neurons’ weights are ...finding by solving linear programming formulations.•The designed classifier shows good generalization accuracy for benchmark datasets.•The proposed algorithm can be straight applied to other multi-class classification problems.
In this paper we deal with the problem of designing a classifier able to learn the classification of existing units in inventory and then use it to classify new units according to their attributes in a multi-criteria ABC inventory classification environment. To solve this problem we design a multi-start constructive algorithm to train a discrete artificial neural network using a randomized greedy strategy to add neurons to the network hidden layer. The process of weights’ searching for the neurons to be added is based on solving linear programming formulations. The computational experiments show that the proposed algorithm is much more efficient when the dual formulations are used to find the weights of the network neurons and that the obtained classifier has good levels of generalization accuracy. In addition, the proposed algorithm can be straight applied to other multi-class classification problems with more than three classes.
Neonatal abstinence syndrome (NAS) incidence has significantly increased in the US in recent years. It is therefore important to develop effective intervention protocols that mitigate the long-term ...consequences of this condition for the mother, her child, and the community.
We used Monte Carlo simulation to estimate the impact of four interventions for NAS and their combinations on pregnant women with opioid use disorder. The key outputs were changes in incremental costs from baseline from the Medicaid perspective and from a total systems perspective and effect size changes. Simulation parameters and costs were based on the literature and baseline model validation was performed using Medicaid claims for Indiana.
Compared to baseline, the resulting simulation estimates showed that three interventions significantly decreased Medicaid incremental costs by 8% (mandatory opioid testing (MOT)), 4% (patient navigators), and 3% (peer recovery coaches). The combination of the three interventions reduced Medicaid direct costs by 26%. Reductions were similar for total system incremental costs (ranging from 2 to 24%), though MOT was found to increase costs of overdose death based on productivity loss. NAS case reductions ranged from 1% (capacity change) to 13% (MOT).
Using systems-based modeling, we showed that costs associated with NAS can be significantly reduced. However, effective implementation would require the involvement and coordination of several stakeholders. In addition, careful protocols for MOT should be considered to ensure pregnant women don't forgo prenatal care for fear of punitive consequences.
Strong evidence exists based on metanalysis of the relationship between toxoplasmosis and many psychiatric diseases: schizophrenia, bipolar disorder, and suicidal behavior. Herein, we estimate the ...number of cases based on the attributable fraction due to toxoplasmosis on these diseases. The population attributable fraction of mental disease associated with toxoplasmosis was 20,4% for schizophrenia; 27,3% for bipolar disorder; and 0,29% for suicidal behavior (self-harm). The lower and upper estimated number of people with mental disease associated with toxoplasmosis was 4′816.491 and 5′564.407 for schizophrenia; 6′348.946 and 7′510.118,82 for bipolar disorder; and 24.310 and 28.151 for self-harm; for a global total lower estimated number of 11′189.748 and global total upper estimated number of 13′102.678 people with mental disease associated with toxoplasmosis for the year 2019. According to the prediction through the Bayesian model of risk factors for toxoplasmosis associated with mental disease, these varied in importance geographically; thus, in Africa, the most important risk factor was water contamination and in the European region, the cooking conditions of meats. Toxoplasmosis and mental health should be a research priority given the enormous potential impact of reducing this parasite in the general population.
The von Hippel-Lindau (VHL) protein serves as the substrate recognition subunit of the multi-subunit Cullin-2 RING E3 ubiquitin ligase (CRL2
VHL
), which regulates intracellular concentrations of ...hypoxia inducible factors (HIFs) through a ubiquitin proteasome system (UPS) cascade. Strategic recruitment of CRL2
VHL
by bi- or trifunctional targeted protein degraders (
e.g.
, PROTACs®) offers the prospect of promoting aberrant polyubiquitination and ensuing proteasomal degradation of disease-related proteins. Non-peptidic,
l
-hydroxyproline-bearing VHL ligands such as VH032 (
1
) and its chiral benzylic amine analog Me-VH032 (
2
), are functional components of targeted protein degraders commonly employed for this purpose. Herein, we compare two approaches for the preparation of
1
and
2
primarily highlighting performance differences between Pd(OAc)
2
and Pd-PEPPSI-IPr for the key C-H arylation of 4-methylthiazole. Results from this comparison prompted the development of a unified, five-step route for the preparation of either VH032 (
1
) or Me-VH032 (
2
) in multigram quantities, resulting in yields of 56% and 61% for
1
and
2
, respectively. Application of
N
-Boc-
l
-4-hydroxyproline rather than
N-tert
-butoxycarbonyl to shield the benzylic amine during the coupling step enhances step economy. Additionally, we identified previously undisclosed minor byproducts generated during arylation steps along with observations from amine deprotection and amidation reaction steps that may prove helpful not only for the preparation of
1
and
2
, but for other VHL recruiting ligands, as well.
Step economical routes for the multigram preparation of popular VHL E3 ligase recruiting ligands.
The Neuro-Psycho-Pathology Center (NPPC) in the Democratic Republic of Congo is a 450-bed neuropsychiatric clinic that pioneered efforts to synergize various disciplines: neurology, neurosurgery, ...neuropsychiatry, and psychiatry. It serves the brain and behavioral health needs of Congolese patients, and at its peak, the NPPC was a major domestic neuropsychiatry center that averaged 320 admissions annually. Financial and resources shortages have curtailed its functions at 10% of its real capacity. Our report accounts the NPPC’s early vision, and we also highlight the ongoing challenges faced by this institution.
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