Evaluating the Integration of Chromosomal Microarray Analysis with Karyotyping for Improved Detection of Chromosomal Abnormalities in Recurrent Pregnancy Loss: A Meta-Narrative Review

Investigating genetic abnormalities in recurrent pregnancy loss (RPL) is critical due to the large number of unexplained cases, which account for around 50%. While routine karyotyping of products of conception (POC) is widely employed, its efficacy is limited by a high failure rate in cytogenetics laboratories. Thus, Chromosomal Microarray Analysis (CMA) offers a potential option, with a success rate of more than 90% when karyotyping fails. Unlike karyotyping, CMA allows a full genome investigation without the requirement for live cultures, allowing the discovery of a variety of genetic abnormalities linked to pregnancy loss, including copy number variations, deletions, duplications, and aneuploidy. These abnormalities are prevalent, representing 47.4% of first-trimester losses and 10.9% of second and third-trimester losses. Therefore, this study seeks to increase diagnostic accuracy and identify genetic variables contributing to RPL by evaluating the efficacy of combining CMA and karyotyping. This meta-narrative review serves to evaluate this combined approach as an improved method for developing individualized treatment programs and providing support to afflicted individuals and couples.https://openworks.mdanderson.org/rmps24/1008/thumbnail.jp

Should physical activity recommendations be ethnicity-specific? Evidence from a cross-sectional study of south Asian and European men

Background Expert bodies and health organisations recommend that adults undertake at least 150 min.week−1 of moderate-intensity physical activity (MPA). However, the underpinning data largely emanate from studies of populations of European descent. It is unclear whether this level of activity is appropriate for other ethnic groups, particularly South Asians, who have increased cardio-metabolic disease risk compared to Europeans. The aim of this study was to explore the level of MPA required in South Asians to confer a similar cardio-metabolic risk profile to that observed in Europeans undertaking the currently recommended MPA level of 150 min.week−1.<p></p> Methods Seventy-five South Asian and 83 European men, aged 40–70, without cardiovascular disease or diabetes had fasted blood taken, blood pressure measured, physical activity assessed objectively (using accelerometry), and anthropometric measures made. Factor analysis was used to summarise measured risk biomarkers into underlying latent ‘factors’ for glycaemia, insulin resistance, lipid metabolism, blood pressure, and overall cardio-metabolic risk. Age-adjusted regression models were used to determine the equivalent level of MPA (in bouts of ≥10 minutes) in South Asians needed to elicit the same value in each factor as Europeans undertaking 150 min.week−1 MPA.<p></p> Findings For all factors, except blood pressure, equivalent MPA values in South Asians were significantly higher than 150 min.week−1; the equivalent MPA value for the overall cardio-metabolic risk factor was 266 (95% CI 185-347) min.week−1.<p></p> Conclusions South Asian men may need to undertake greater levels of MPA than Europeans to exhibit a similar cardio-metabolic risk profile, suggesting that a conceptual case can be made for ethnicity-specific physical activity guidance. Further study is needed to extend these findings to women and to replicate them prospectively in a larger cohort.<p></p&gt

Brain stem tumors in children less than 3 months: Clinical and radiologic findings of a rare disease

\ua9 The Author(s) 2024.Purpose: Brain stem tumors in children < 3 months at diagnosis are extremely rare. Our aim is to study a retrospective cohort to improve the understanding of the disease course and guide patient management. Methods: This is a multicenter retrospective analysis across the European Society for Pediatric Oncology SIOP-E HGG/DIPG Working Group linked centers, including patients with a brainstem tumor diagnosed between 2009 and 2020 and aged < 3 months at diagnosis. Clinical data were collected, and imaging characteristics were analyzed blindly and independently by two neuroradiologists. Results: Five cases were identified. No patient received any therapy. The epicenter of two tumors was in the medulla oblongata alone and in the medulla oblongata and the pons in three. For patients with tumor in equal parts in the medulla oblongata and the pons (n = 3), the extension at diagnosis involved the spinal cord; for the two patients with the tumor epicenter in the medulla oblongata alone (n = 2), the extension at diagnosis included the pons (n = 2) and the spinal cord (n = 1). Biopsy was performed in one patient identifying a pilocytic astrocytoma. Two patients died. In one patient, autopsy revealed a high-grade glioma (case 3). Three survivors showed either spontaneous tumor regression (n = 2) or stable disease (n = 1). Survivors were followed up for 10, 7, and 0.6 years, respectively. One case had the typical imaging characteristics of a dorsal exophytic low-grade glioma. Conclusions: No patient fulfilled the radiologic criteria defining a high-grade glioma. Central neuroradiological review and biopsy may provide useful information regarding the patient management

Domain walls in three dimensional gauged supergravity

We explicitly construct two Chern-Simons gauged supergravities in three dimensions with N=4 and N=8 supersymmetries and non-semisimple gauge groups. The N=4 theory has scalar manifold $SO(4,3)/SO(4)\times SO(3)$ with the gauge group $SO(3)\ltimes (\mathbf{T}^3,\hat{\mathbf{T}}^3)$. The theory describes (1,0) six dimensional supergravity reduced on an SU(2) group manifold. The equivalent Yang-Mills type gauged supergravity has SO(3) gauge group coupled to three massive vector fields. The N=8 theory is described by $SO(8,8)/SO(8)\times SO(8)$ scalar manifold, and the gauge group is given by $SO(8)\ltimes \mathbf{T}^{28}$. The theory is a truncation of the $SO(8)\ltimes \mathbf{T}^{28}$ gauged N=16 theory with scalar manifold $E_{8(8)}/SO(16)$ and can be obtained by an S^7 compactification of type I theory in ten dimensions. Domain wall solutions of both gauged supergravities are analytically found and can be uplifted to higher dimensions. These provide domain wall vacua in the three dimensional gauged supergravity framework which might be useful for the study of Domain Wall$_3$/QFT$_2$ correspondence.Comment: 19 pages, no figures, typoes and a mistake in a sign corrected, clarifications on the notations adde

Towards third generation matrix metalloproteinase inhibitors for cancer therapy

The failure of matrix metalloproteinase (MMP) inhibitor drug clinical trials in cancer was partly due to the inadvertent inhibition of MMP antitargets that counterbalanced the benefits of MMP target inhibition. We explore how MMP inhibitor drugs might be developed to achieve potent selectivity for validated MMP targets yet therapeutically spare MMP antitargets that are critical in host protection

Cavity mode enhancement of terahertz emission from equilateral triangular microstrip antennas of the high-TcT_c superconductor Bi2_2Sr2_2CaCu2_2O8+δ_{8 + δ}

We study the transverse magnetic (TM) electromagnetic cavity mode wave functions for an ideal equilateral triangular microstrip antenna (MSA) exhibiting $C_{3v}$ point group symmetry. When the $C_{3v}$ operations are imposed upon the antenna, the TM($m,n$) modes with wave vectors $\alpha \sqrt[ ]{m^2 + nm + n^2}$ are much less dense than commonly thought. The $R_3$ operations restrict the integral $n$ and $m$ to satisfy $\mid m - n \mid$ = 3$p$, where $p \geq$ 0 and $p \geq$ 1 for the modes even and odd under reflections about the three mirror planes, respectively. We calculate the forms of representative wave functions and the angular dependence of the output power when these modes are excited by the uniform and non-uniform ac Josephson current sources in thin, ideally equilateral triangular MSAs employing the intrinsic Josephson junctions in the high transition temperature $T_c$ superconductor Bi$_2$Sr$_2$CaCu$_2$O$_{8 + \delta}$, and fit the emissions data from an earlier sample for which the $C_{3v}$ symmetry was apparently broken.UCF RAMP program, JSPS Research Fellowship for young scientists, CREST-JST (Japan Science and Technology Agency), WPI (World Premier International Research Center Initiative)- MANA (Materials Nanoarchitectonics) project (NIMS

Cavity mode enhancement of terahertz emission from equilateral triangular microstrip antennas of the high-TcT_c superconductor Bi2_2Sr2_2CaCu2_2O8+δ_{8 + δ}

We study the transverse magnetic (TM) electromagnetic cavity mode wave functions for an ideal equilateral triangular microstrip antenna (MSA) exhibiting $C_{3v}$ point group symmetry. When the $C_{3v}$ operations are imposed upon the antenna, the TM($m,n$) modes with wave vectors $\alpha \sqrt[ ]{m^2 + nm + n^2}$ are much less dense than commonly thought. The $R_3$ operations restrict the integral $n$ and $m$ to satisfy $\mid m - n \mid$ = 3$p$, where $p \geq$ 0 and $p \geq$ 1 for the modes even and odd under reflections about the three mirror planes, respectively. We calculate the forms of representative wave functions and the angular dependence of the output power when these modes are excited by the uniform and non-uniform ac Josephson current sources in thin, ideally equilateral triangular MSAs employing the intrinsic Josephson junctions in the high transition temperature $T_c$ superconductor Bi$_2$Sr$_2$CaCu$_2$O$_{8 + \delta}$, and fit the emissions data from an earlier sample for which the $C_{3v}$ symmetry was apparently broken.UCF RAMP program, JSPS Research Fellowship for young scientists, CREST-JST (Japan Science and Technology Agency), WPI (World Premier International Research Center Initiative)- MANA (Materials Nanoarchitectonics) project (NIMS

The Effects of Dasatinib in Experimental Acute Respiratory Distress Syndrome Depend on Dose and Etiology

Background/Aims: Evidence suggests that tyrosine-kinase inhibitors may attenuate lung inflammation and fibrosis in experimental acute respiratory distress syndrome (ARDS). We hypothesized that dasatinib, a tyrosine-kinase inhibitor, might act differently depending on the ARDS etiology and the dose. Methods: C57/BL6 mice were divided to be pre-treated with dasatinib (1mg/kg or 10mg/kg) or vehicle (1% dimethyl-sulfoxide) by oral gavage. Thirty-minutes after pre-treatment, mice were subdivided into control (C) or ARDS groups. ARDS animals received Escherichia coli lipopolysaccharide intratracheally (ARDSp) or intraperitoneally (ARDSexp). A new dose of dasatinib or vehicle was administered at 6 and 24h. Results: Forty-eight hours after ARDS induction, dasatinib 1mg/kg yielded: improved lung morphofunction and reduced cells expressing toll-like receptor (TLR)-4 in lung, independent of ARDS etiology; reduced neutrophil and levels of interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-β in ARDSp. The higher dose of dasatinib caused no changes in lung mechanics, diffuse alveolar damage, neutrophil, or cells expressing TLR4, but increased IL-6, vascular endothelial growth factor (VEGF), and cells expressing Fas receptor in lung in ARDSp. In ARDSexp, it improved lung morphofunction, increased VEGF, and reduced cells expressing TLR4. Conclusion: Dasatinib may have therapeutic potential in ARDS independent of etiology, but careful dose monitoring is required. © 2015 S. Karger AG, Basel

Guanidine-Catalyzed Reductive Amination of Carbon Dioxide with Silanes: Switching between Pathways and Suppressing Catalyst Deactivation

A mechanistic investigation into the guanidine-catalyzed reductive amination of CO₂, using a combination of ¹H, ²⁹Si NMR, FT-IR, MS, and GC profiling, is reported. Inexpensive and readily available N,N,N′,N′-tetramethylguanidine (TMG) was found to be an equally effective catalyst compared to more elaborate cyclic guanidines. Different catalytic pathways to formamide 2, aminal 4, and N-methylamine 3 were identified. A pathway to formamide product 2 dominates at 23 °C. Increasing the reaction temperature to 60 °C enables a competitive, higher-energy pathway to 4 and 3, which requires direct reduction of CO₂ with PhSiH₃ to formoxysilane E. Reduction of aminal 4, in the presence of CO₂ and the catalyst, led to formation of a 1:1 ratio of 2 and 3. The catalyst itself can be formylated under the reaction conditions, resulting in its deactivation. Thus, alkylated TMGs were found to be more stable and more active catalysts than TMG, leading to a successful organocatalyzed reductive functionalization of CO₂ with silane at 0.1 mol % catalyst loading (TON = 805 and TOF = 33.5 h‾¹)

Lower cardiorespiratory fitness contributes to increased insulin resistance and fasting glycaemia in middle-aged South Asian compared with European men living in the UK

AIMS/HYPOTHESIS: This study aimed to determine the extent to which increased insulin resistance and fasting glycaemia in South Asian men, compared with white European men, living in the UK, was due to lower cardiorespiratory fitness (maximal oxygen uptake [[Formula: see text]]) and physical activity. METHODS: One hundred South Asian and 100 age- and BMI-matched European men without diagnosed diabetes, aged 40–70 years, had fasted blood taken for measurement of glucose concentration, HOMA-estimated insulin resistance (HOMA(IR)), plus other risk factors, and underwent assessment of physical activity (using accelerometry), [Formula: see text], body size and composition, and demographic and other lifestyle factors. For 13 South Asian and one European man, HbA(1c) levels were >6.5% (>48 mmol/mol), indicating potential undiagnosed diabetes; these men were excluded from the analyses. Linear regression models were used to determine the extent to which body size and composition, fitness and physical activity variables explained differences in HOMA(IR) and fasting glucose between South Asian and European men. RESULTS: HOMA(IR) and fasting glucose were 67% (p < 0.001) and 3% (p < 0.018) higher, respectively, in South Asians than Europeans. Lower [Formula: see text], lower physical activity and greater total adiposity in South Asians individually explained 68% (95% CI 45%, 91%), 29% (11%, 46%) and 52% (30%, 80%), respectively, and together explained 83% (50%, 119%) (all p < 0.001) of the ethnic difference in HOMA(IR). Lower [Formula: see text] and greater total adiposity, respectively, explained 61% (9%, 111%) and 39% (9%, 76%) (combined effect 63% [8%, 115%]; all p < 0.05) of the ethnic difference in fasting glucose. CONCLUSIONS/INTERPRETATION: Lower cardiorespiratory fitness is a key factor associated with the excess insulin resistance and fasting glycaemia in middle-aged South Asian, compared with European, men living in the UK. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-013-2969-y) contains peer-reviewed but unedited supplementary material, which is available to authorised users