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Zeolitic imidazolate frameworks are a class of metal-organic frameworks that are topologically isomorphic with zeolites. Zeolitic imidazolate frameworks are composed of tetrahedrally coordinated metal ions connected by imidazolate linkers and have a high porosity and chemical stability. Here, we summarize the progress made in the application of zeolitic imidazolate frameworks in sample preparation for analytical purposes. This review is focused on analytical methods based on liquid chromatography, gas chromatography, or capillary electrophoresis, where the use of zeolitic imidazolate frameworks has contributed to increasing the sensitivity and selectivity of the method. While bulk zeolitic imidazolate frameworks have been directly used in analytical sample preparation protocols, a variety of strategies for their magnetization or their incorporation into sorbent particles, monoliths, fibers, stir bars, or thin films, have been developed. These modifications have facilitated the handling and application of zeolitic imidazolate frameworks for a number of analytical sample treatments including magnetic solid-phase extraction, solid-phase microextraction, stir bar sorptive extraction, or thin film microextraction, among other techniques.More than half of patients with hypertension require two or more medicines to control blood pressure. Combinations of anti-hypertensive medicines are available as Single Pill Combinations (SPCs) or Single Agent Pills (SAPs). SPCs of two or more anti-hypertensive medicines facilitate simpler dosing schedules, decrease pill burden, increase adherence to medicine, and simplify procurement and distribution. Despite this, equivalent combinations of separate pills (SAPs) are often prescribed instead of SPCs under the assumption that SAPs are priced lower. This study compared prices of anti-hypertensive SPCs and equivalent SAPs in the private health care sector of India. High sales volume anti-hypertensive SPCs and SAPs were selected from 2018 private sector pharmaceutical sales data. SPCs and SAPs price information was collected from online pharmacy websites between November 2019 and January 2020. Anti-hypertensive SPCs represent approximately 39.1% of India’s private sector anti-hypertensive drug market. Multiple manufacturers produce the same top-selling SPCs, suggesting a viable and competitive market. A comparison of SPCs and SAPs across different manufacturers showed that the lowest prices of both SPCs and the sum of component SAPs were nearly identical across different manufacturers. An analysis of dual-drug SPCs and SAPs by the same manufacturer showed that most manufacturers (five of six) had priced their SPCs higher than SAPs. selleck compound These observations suggest that the price of SPCs could be lowered to match the combined price of the component SAPs, and manufacturing costs and market forces do not present a barrier to the implementation of anti-hypertensive SPCs.Large-scale genetic studies revealed SCN2A as one of the most frequently mutated genes in patients with neurodevelopmental disorders. SCN2A encodes for the voltage-gated sodium channel isoform 1.2 (Nav 1.2) expressed in the neurons of the central nervous system. Homozygous knockout (null) of Scn2a in mice is perinatal lethal, whereas heterozygous knockout of Scn2a (Scn2a+/- ) results in mild behavior abnormalities. The Nav 1.2 expression level in Scn2a+/- mice is reported to be around 50-60% of the wild-type (WT) level, which indicates that a close to 50% reduction of Nav 1.2 expression may not be sufficient to lead to major behavioral phenotypes in mice. To overcome this barrier, we characterized a novel mouse model of severe Scn2a deficiency using a targeted gene-trap knockout (gtKO) strategy. link2 This approach produces viable homozygous mice (Scn2agtKO/gtKO ) that can survive to adulthood, with about a quarter of Nav 1.2 expression compared to WT mice. Innate behaviors like nesting and mating were profoundly disrupted in Scn2agtKO/gtKO mice. Notably, Scn2agtKO/gtKO mice have a significantly decreased center duration compared to WT in the open field test, suggesting anxiety-like behaviors in a novel, open space. These mice also have decreased thermal and cold tolerance. Additionally, Scn2agtKO/gtKO mice have increased fix-pattern exploration in the novel object exploration test and a slight increase in grooming, indicating a detectable level of repetitive behaviors. They bury little to no marbles and have decreased interaction with novel objects. These Scn2a gene-trap knockout mice thus provide a unique model to study pathophysiology associated with severe Scn2a deficiency.Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder caused by lack of the paternal copy of maternally imprinted, paternally expressed genes at the chromosome 15q11-13 region. In most cases, it is caused by a paternal deletion or a maternal disomy of chromosome 15. Behavioral problems with temper outbursts are common and often combined with physical aggressiveness and self-injury. They are the most frequent cause for a reduced quality of life in adulthood and represent a serious challenge for the individual and those surrounding the individual in everyday life. Until now, no promising pharmaceutical treatment option has been established, and only a few case reports on treatment with selective serotonin reuptake inhibitors (SSRIs) have been reported. In this case series, we investigated the effect of the SSRI sertraline in 14 individuals with PWS frequently showing severe temper outbursts with aggressiveness and self-injuries. After 6 months of treatment with sertraline, 13 of 14 patients (92.6%) either no longer displayed temper outbursts or showed a significant decrease in frequency and severity of temper outbursts. In one case, treatment was stopped due to severe sleep abnormalities. We conclude that sertraline is a promising and safe treatment option for severe temper outbursts in patients with PWS.Andersen-Tawil syndrome (ATS) is a rare potassium channelopathy causing periodic paralysis, cardiac arrhythmias, and dysmorphic features. A detailed analysis of the face could facilitate diagnosis of ATS, as approximately 30% of patients do not show variants in KCNJ2 gene, and diagnosis is established by clinical findings. We aimed to characterize the face in ATS through a quantitative approach, as facial anomalies may be unnoticed on visual inspection. Facial images of 12 subjects with genetically confirmed ATS (six males, six females, age 5-67 years) were acquired through stereophotogrammetry. Using 38 soft-tissue landmarks, linear distances, angles, and ratios were calculated and expressed as z-score values, with reference to 477 healthy subjects matched for sex and age. All patients showed decreased lower facial height with shortening of philtrum (mean z-score ± SD -1.5 ± 0.9), smaller mid and lower facial depths (-1.9 ± 0.7; -2.3 ± 0.9), short palpebral fissures (right -1.2 ± 0.4; left -1.6 ± 0.6), smaller mandibular ramus length (-2.1 ± 0.4), and increased nasal width/length ratio (1.4 ± 0.5) with smaller nostril axis length (right -1.8 ± 0.8, left -1.6 ± 0.7). Hypertelorism and low-set ears were detected in two-thirds of patients. The study quantified facial dysmorphysm in ATS, extending information about known features, and detecting unrecorded philtrum and nostril characteristics, which may be distinctive traits of the disorder.

The aim of this study was to identify the risk factors and prognosis of patients with cancer-associated myositis (CAM).

Four hundred and eighty-seven patients with dermatomyositis (DM), clinical amyopathic dermatomyositis (CADM) and polymyositis (PM) from 3 clinical centers were enrolled retrospectively in this study. Clinical and laboratory data of CAM and non-CAM patients were compared. Logistic regression analysis was used to identify risk factors of CAM.

Out of the 487 patients with DM/CADM/PM, 7.0% (34/487) of patients were classified as CAM. Older age (53.91±13.32 vs. 48.76±14.34years), heliotrope rash (61.8% vs. 41.9%), shawl sign (41.2% vs. 22.1%), V sign (58.8% vs. link3 38.6%) were observed significantly more commonly in patients with CAM than those without CAM (all P<.05). Fever (17.7% vs. 37.8%), arthralgia/arthritis (23.5% vs. 45.7%), interstitial lung disease (ILD, 38.2% vs 68.9%) were significantly less common in the CAM group than the non-CAM group. Age at onset (odds ratio [OR] 1.036, 95% CI 1.001-1.072, P=.042), shawl sign (OR 2.748, 95% CI 1.107-6.822, P=.029), anti-transition initiation factor (TIF)-1γ antibody (OR 4.012, 95% CI 1.268-12.687, P=.018) were identified as the initial risk factors for the onset of CAM, and ILD was identified as a protective factor for CAM (OR 0.292, 95% CI 0.115-0.739, P=.009). All-cause mortality was significantly higher in CAM patients compared with non-CAM patients (P=.001).

The mortality of patients with CAM was higher than DM/CADM/PM patients without cancer. Malignancy should be screened in DM/CADM/PM patients especially with risk factors, including older age, shawl sign, anti-TIF-1γ antibody, and lack of ILD.

The mortality of patients with CAM was higher than DM/CADM/PM patients without cancer. Malignancy should be screened in DM/CADM/PM patients especially with risk factors, including older age, shawl sign, anti-TIF-1γ antibody, and lack of ILD.The brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) polymorphism has been shown to moderate the extent to which memory decline manifests in preclinical Alzheimer’s disease (AD). To date, no study has examined the relationship between BDNF and memory in individuals across biologically confirmed AD clinical stages (i.e., Aβ+). We aimed to understand the effect of BDNF on episodic memory decline and clinical disease progression over 126 months in individuals with preclinical, prodromal and clinical AD. Participants enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study who were Aβ + (according to positron emission tomography), and cognitively normal (CN; n = 238), classified as having mild cognitive impairment (MCI; n = 80), or AD (n = 66) were included in this study. Cognition was evaluated at 18 month intervals using an established episodic memory composite score over 126 months. We observed that in Aβ + CNs, Met66 was associated with greater memory decline with increasing age and were 1.5 times more likely to progress to MCI/AD over 126 months. In Aβ + MCIs, there was no effect of Met66 on memory decline or on disease progression to AD over 126 months. In Aβ + AD, Val66 homozygotes showed greater memory decline, while Met66 carriers performed at a constant and very impaired level. Our current results illustrate the importance of time and disease severity to clinicopathological models of the role of BDNF Val66Met in memory decline and AD clinical progression. Specifically, the effect of BDNF on memory decline is greatest in preclinical AD and reduces as AD clinical disease severity increases.Central nervous system (CNS) involvement is a serious but often underdiagnosed complication of hematological malignancies. Currently, the gold standard to detect CNS involvement is conventional cytology (CC) whose sensitivity though is lower than 50%. Multiparametric flow cytometry (MFC) demonstrated a superior sensitivity over CC, particularly when low levels of CNS infiltrating cells are present. Although prospective studies are few, a positive finding by MFC appears to anticipate an adverse outcome even if CC shows no infiltration. However, the use of MFC to diagnose CNS involvement presents some pitfalls, due to the typical hypocellularity of cerebrospinal fluids (CSF), and low cell vitality. Furthermore, the threshold to be used for defining the MFC positivity is not universally defined. In this paper, a working group of the European Society for Clinical Cell Analysis-ESCCA-and the Italian Society for Clinical Cell Analysis-ISCCA-will discuss the critical aspects of CSF processing, highlighting difficulties in storage and processing of samples, interpretation and reporting of data.