Maturity‐onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance.
GCK
‐MODY and
HNF1A
‐MODY are the prevalent subtypes. Currently, there is growing ...concern regarding the correct interpretation of molecular genetic findings. The American College of Medical Genetics and Genomics (ACMG) updated guidelines to interpret and classify molecular variants. This study aimed to determine the prevalence of MODY (
GCK
/
HNF1A
) in a large cohort of Brazilian families, to report variants related to phenotype, and to classify them according to ACMG guidelines. One hundred and nine probands were investigated, 45% with clinical suspicion of
GCK
‐MODY and 55% with suspicion of
HNF1A
‐MODY. Twenty‐five different variants were identified in
GCK
gene (30 probands—61% of positivity), and 7 variants in
HNF1A
(10 probands—17% of positivity). Fourteen of them were novel (12—
GCK
/2—
HNF1A
). ACMG guidelines were able to classify a large portion of variants as pathogenic (36%—
GCK
/86%—
HNF1A
) and likely pathogenic (44%—
GCK
/14%—
HNF1A
), with 16% (5/32) as uncertain significance. This allows us to determine the pathogenicity classification more efficiently, and also reinforces the suspected associations with the phenotype among novel variants.
While several studies have observed that solid organ transplant recipients experience diminished antibody responses to SARS-CoV-2 mRNA vaccination, data specific to heart and lung transplant (HT/LT) ...recipients remains sparse.
US adult HT and LT recipients completed their vaccine series between January 7 and April 10, 2021. Reactogencity and SARS-CoV-2 anti-spike antibody were assessed after a priming dose (D1) and booster dose (D2). Modified Poisson regression with robust variance estimator was used to evaluate associations between participant characteristics and antibody development.
Of 134 heart recipients, there were 38% non-responders (D1-/D2-), 48% booster responders (D1-/D2+), and 14% priming dose responders (D1+/D2+). Of 103 lung recipients, 64% were non-responders, 27% were booster responders, and 9% were priming dose responders. Lung recipients were less likely to develop antibodies (p < .001). Priming dose antibody response was associated with younger recipient age (p = .04), transplant-to-vaccination time ≥6 years (p < .01), and lack of anti-metabolite maintenance immunosuppression (p < .001). Pain at injection site was the most commonly reported reaction (85% after D1, 76% after D2). Serious reactions were rare, the most common being fatigue (2% after D1 and 3% after D2). No serious adverse events were reported.
HT and LT recipients experienced diminished antibody response following vaccination; reactogenicity was comparable to that of the general population. LT recipients may exhibit a more impaired antibody response than HT recipients. While current recommendations are to vaccinate eligible candidates and recipients, further studies characterizing the cell-mediated immune response and clinical efficacy of these vaccines in this population are needed.
To review the growth and current penetration of ICU telemedicine programs, association with outcomes, studies of their impact on medical education, associations with medicolegal risks, identify ...program revenue sources and costs, regulatory aspects, and the ICU telemedicine research agenda.
Review of the published medical literature, governmental documents, and opinions of experts from the Society of Critical Care Medicine ICU Telemedicine Committee.
Formal ICU telemedicine programs now support 11% of nonfederal hospital critically ill adult patients. There is increasingly robust evidence of association with lower ICU (0.79; 95% CI, 0.65-0.96) and hospital mortality (0.83; 95% CI, 0.73-0.94) and shorter ICU (-0.62 d; 95% CI, -1.21 to -0.04 d) and hospital (-1.26 d; 95% CI, -2.49 to -0.03 d) length of stay. Physicians in training report experiences with telemedicine intensivists that are positive and increased patient safety. Early studies suggest that implementation of ICU telemedicine programs has been associated with lower numbers of malpractice claims and costs. The requirements for Medicare reimbursement and states with legislation addressing providing professional services by telemedicine are detailed.
The inclusion of an ICU telemedicine program as a major part of their critical care delivery paradigm has been implemented for 11% of critically ill U.S. adults as a solution for the problem of access to adult critical care services. Implementation of an ICU telemedicine program is one practical way to increase access and reduce mortality as well as length of stay. ICU telemedicine research including comparative effectiveness studies is urgently needed.
Galectin-3 is a β-galactoside—binding lectin widely expressed on epithelial and hematopoietic cells, and its expression is frequently associated with a poor prognosis in cancer. Because it has not ...been well-studied in human infectious disease, we examined galectin-3 expression in mycobacterial infection by studying leprosy, an intracellular infection caused by Mycobacterium leprae. Galectin-3 was highly expressed on macrophages in lesions of patients with the clinically progressive lepromatous form of leprosy; in contrast, galectin-3 was almost undetectable in self-limited tuberculoid lesions. We investigated the potential function of galectin-3 in cell-mediated immunity using peripheral blood monocytes. Galectin-3 enhanced monocyte interleukin 10 production to a TLR2/1 ligand, whereas interleukin 12p40 secretion was unaffected. Furthermore, galectin-3 diminished monocyte to dendritic cell differentiation and T-cell antigen presentation. These data demonstrate an association of galectin-3 with unfavorable host response in leprosy and a potential mechanism for impaired host defense in humans.
Abstract Introduction Great ventilation to carbon dioxide output (Δ V ˙ E/Δ V ˙ CO2 ) and reduced end-tidal partial pressures for CO2 (P et CO2 ) during incremental exercise are hallmarks of chronic ...thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (IPAH). However, CTEPH is more likely to involve proximal arteries, which may lead to poorer right ventricle–pulmonary vascular coupling and worse gas exchange abnormalities. Therefore, abnormal P et CO2 profiles during exercise may be more prominent in patients with CTEPH and could be helpful to indicate disease severity. Methods Seventy patients with CTEPH and 34 with IPAH underwent right heart catheterization and cardiopulmonary exercise testing. According to P et CO2 pattern during exercise, patients were classified as having an increase or stabilization in P et CO2 up to the gas exchange threshold (GET), an abrupt decrease in the rest-exercise transition or a progressive and slow decrease throughout exercise. A subgroup of patients with CTEPH underwent a constant work rate exercise test to obtain arterial blood samples during steady-state exercise. Results Multivariate logistic regression analyses showed that progressive decreases in P et CO2 and SpO2 were better discriminative parameters than Δ V ˙ E/Δ V ˙ CO2 to distinguish CTEPH from IPAH. This pattern of P et CO2 was associated with worse functional impairment and greater reduction in PaCO2 during exercise. Conclusion Compared to patients with IPAH, patients with CTEPH present more impaired gas exchange during exercise, and P et CO2 abnormalities may be used to identify more clinically and hemodynamically severe cases.
ABSTRACT
Strong lensing is a powerful probe of the matter distribution in galaxies and clusters and a relevant tool for cosmography. Analyses of strong gravitational lenses with deep learning have ...become a popular approach due to these astronomical objects’ rarity and image complexity. Next-generation surveys will provide more opportunities to derive science from these objects and an increasing data volume to be analysed. However, finding strong lenses is challenging, as their number densities are orders of magnitude below those of galaxies. Therefore, specific strong lensing search algorithms are required to discover the highest number of systems possible with high purity and low false alarm rate. The need for better algorithms has prompted the development of an open community data science competition named strong gravitational lensing challenge (SGLC). This work presents the deep learning strategies and methodology used to design the highest scoring algorithm in the second SGLC (II SGLC). We discuss the approach used for this data set, the choice of a suitable architecture, particularly the use of a network with two branches to work with images in different resolutions, and its optimization. We also discuss the detectability limit, the lessons learned, and prospects for defining a tailor-made architecture in a survey in contrast to a general one. Finally, we release the models and discuss the best choice to easily adapt the model to a data set representing a survey with a different instrument. This work helps to take a step towards efficient, adaptable, and accurate analyses of strong lenses with deep learning frameworks.
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