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1.
FASEB J ; 38(14): e23842, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39037554

ABSTRACT

G-protein-coupled receptors (GPCRs) belonging to the type 2 taste receptors (TAS2Rs) family are predominantly present in taste cells to allow the perception of bitter-tasting compounds. TAS2Rs have also been shown to be expressed in human airway smooth muscle (ASM), and TAS2R agonists relax ASM cells and bronchodilate airways despite elevating intracellular calcium. This calcium "paradox" (calcium mediates contraction by pro-contractile Gq-coupled GPCRs) and the mechanisms by which TAS2R agonists relax ASM remain poorly understood. To gain insight into pro-relaxant mechanisms effected by TAS2Rs, we employed an unbiased phosphoproteomic approach involving dual-mass spectrometry to determine differences in the phosphorylation of contractile-related proteins in ASM following the stimulation of cells with TAS2R agonists, histamine (an agonist of the Gq-coupled H1 histamine receptor) or isoproterenol (an agonist of the Gs-coupled ß2-adrenoceptor) alone or in combination. Our study identified differential phosphorylation of proteins regulating contraction, including A-kinase anchoring protein (AKAP)2, AKAP12, and RhoA guanine nucleotide exchange factor (ARHGEF)12. Subsequent signaling analyses revealed RhoA and the T853 residue on myosin light chain phosphatase (MYPT)1 as points of mechanistic divergence between TAS2R and Gs-coupled GPCR pathways. Unlike Gs-coupled receptor signaling, which inhibits histamine-induced myosin light chain (MLC)20 phosphorylation via protein kinase A (PKA)-dependent inhibition of intracellular calcium mobilization, HSP20 and ERK1/2 activity, TAS2Rs are shown to inhibit histamine-induced pMLC20 via inhibition of RhoA activity and MYPT1 phosphorylation at the T853 residue. These findings provide insight into the TAS2R signaling in ASM by defining a distinct signaling mechanism modulating inhibition of pMLC20 to relax contracted ASM.


Subject(s)
Muscle, Smooth , Receptors, G-Protein-Coupled , Humans , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/agonists , Muscle, Smooth/metabolism , Muscle, Smooth/drug effects , Phosphorylation , Muscle Relaxation/drug effects , Histamine/metabolism , Histamine/pharmacology , Myosin-Light-Chain Phosphatase/metabolism , Isoproterenol/pharmacology , Calcium/metabolism , rhoA GTP-Binding Protein/metabolism , Taste/physiology , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/drug effects , Signal Transduction , Cells, Cultured
2.
Am J Physiol Lung Cell Mol Physiol ; 327(1): L3-L18, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38742284

ABSTRACT

Signal transduction by G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs) and immunoreceptors converge at the activation of phospholipase C (PLC) for the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). This is a point for second-messenger bifurcation where DAG via protein kinase C (PKC) and IP3 via calcium activate distinct protein targets and regulate cellular functions. IP3 signaling is regulated by multiple calcium influx and efflux proteins involved in calcium homeostasis. A family of lipid kinases belonging to DAG kinases (DGKs) converts DAG to phosphatidic acid (PA), negatively regulating DAG signaling and pathophysiological functions. PA, through a series of biochemical reactions, is recycled to produce new molecules of PIP2. Therefore, DGKs act as a central switch in terminating DAG signaling and resynthesis of membrane phospholipids precursor. Interestingly, calcium and PKC regulate the activation of α and ζ isoforms of DGK that are predominantly expressed in airway and immune cells. Thus, DGK forms a feedback and feedforward control point and plays a crucial role in fine-tuning phospholipid stoichiometry, signaling, and functions. In this review, we discuss the previously underappreciated complex and intriguing DAG/DGK-driven mechanisms in regulating cellular functions associated with asthma, such as contraction and proliferation of airway smooth muscle (ASM) cells and inflammatory activation of immune cells. We highlight the benefits of manipulating DGK activity in mitigating salient features of asthma pathophysiology and shed light on DGK as a molecule of interest for heterogeneous diseases such as asthma.


Subject(s)
Asthma , Diacylglycerol Kinase , Signal Transduction , Asthma/metabolism , Asthma/pathology , Asthma/physiopathology , Asthma/enzymology , Humans , Diacylglycerol Kinase/metabolism , Animals , Diglycerides/metabolism , Protein Kinase C/metabolism
3.
Cureus ; 16(3): e56892, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38659566

ABSTRACT

Gastrointestinal Kaposi's sarcoma (GI-KS), which is frequently observed in individuals with HIV/AIDS, tends to manifest with vague symptoms or may not show any symptoms at all. These symptoms can include abdominal discomfort, nausea, vomiting, and low levels of iron in the blood, and they may worsen as the tumor enlarges, leading to more severe issues such as blockage or perforation of the bowel. Diagnosis usually requires an endoscopy to confirm the presence of GI-SK in individuals showing symptoms. In this case report, we describe a 29-year-old Hispanic male with vague symptomatology, anemia, and a probable unknown bleeding site.

4.
Insects ; 15(3)2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38535353

ABSTRACT

Haemoproteus parasites are the most diverse among Haemosporida. However, their natural vectors (Culicoides) are still poorly investigated and were identified for only a few parasite species and lineages. The application of an integrative approach (insect dissection, microscopic analysis, and molecular-based methods) is necessary in these studies, which have been carried out by a few research groups, mainly in Europe. The aim of this study was (i) to determine the Culicoides species that are naturally infected by Haemoproteus parasites, and which can support its complete sporogonic development, and (ii) to investigate the prevalence of Culicoides species and Haemoproteus parasite lineages in different study sites. In total, 1953 parous Culicoides females, from 11 species, were collected in four different localities in Lithuania and were dissected and analyzed using an integrative approach. The most abundant was C. pictipennis (30.3%). Parasite DNA was found in 7.9% of all investigated Culicoides, of which ~30% had sporozoites in their salivary glands, confirming their vector competence for these parasites. The Botanical Garden presented the highest number of Culicoides parous females, Culicoides species, and parasite lineages, as well as the highest positivity for sporozoites. Culicoides reconditus was confirmed as a natural vector of Haemoproteus parasites, sporozoites of six Haemoproteus lineages were reported for the first time, and 12 new interactions between Haemoproteus parasite lineages and Culicoides species were identified. Haemoproteus parasites seem to be transmitted by a high number of Culicoides species, with C. kibunensis, C. pictipennis, and C. segnis being the most important vectors.

5.
Acta Trop ; 253: 107174, 2024 May.
Article in English | MEDLINE | ID: mdl-38452992

ABSTRACT

Species of subgenus Novyella remain most fragmentarily studied amongst avian malaria agents. Transmission of the recently described Plasmodium (Novyella) homonucleophilum (lineage pSW2) occurs broadly in the Old World, including Europe, however biology of this pathogen remains insufficiently investigated. This study provided the first data on the development of P. homonucleophilum in the experimentally infected Eurasian siskins Spinus spinus exposed by inoculation of infected blood. The parasite strain was isolated from a naturally infected song thrush Turdus philomelos, multiplied in vivo, and inoculated to six Eurasian siskins. The same number of birds were used as negative controls. All exposed birds were susceptible, and the controls remained uninfected during the entire study (172 days). Prepatent period was 8-12 days post exposure (dpe). Maximum parasitaemia reached 50-90 % of infected erythrocytes between 20 and 44 dpe. Then, parasitaemia decreased but remained relatively high during the entire observation. Three of six exposed birds died, indicating high virulence of this infection. The parasitaemia increase coincided with a decline of haematocrit value, indicating anaemia. Polychromasia was evident in all infected birds but not in controls. Body mass of exposed birds increased, coinciding with increased food intake. The latter probably is an adaptation to compensate energy loss of hosts due to the long-lasting parasitism. Exo-erythrocytic stages were not found, suggesting that long-lasting parasitaemia was entirely due to erythrocytic merogony. The lineage pSW2 has been reported broadly in the Old World and is likely a generalist infection. Neglected avian Novyella malaria parasites are worth more attention of researchers due to their cosmopolitan distribution and high virulence.


Subject(s)
Malaria, Avian , Parasites , Plasmodium , Songbirds , Animals , Malaria, Avian/parasitology , Virulence , Songbirds/parasitology , Biology
6.
Heliyon ; 10(4): e26390, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38420396

ABSTRACT

This work aimed to evaluate the growth of two species of microgreens (mizuna and pak choi), using agro-industrial compost as growing media in two different mixes versus one hundred percent peat, under two different LED illumination spectra (LED 1 and LED 2) in a 14 h photoperiod. The experiment was carried-out for two times. Biomass yield, glucosinolates, and phenolic compounds, and nitrate (NO3-) content were analysed in leaf tissues. In both species, the highest fresh and dry biomass production was in compost:peat (50:50%) and LED 2 (Blue/Red/Far Red). In general, compost had a greater influence on nitrate content than light, but in the microgreen pak choi, the anthocyanin content was inhibited by the compost treatment. In the other hand both LED illumination had a positive effect on mizuna for glucosinolates and anthocyanins, and LED 2 also showed a positive effect on pak choi for anthocyanin. Therefore, the use of agri-food compost: peat (50:50%) with LED 2 (blue/red) lighting treatment to obtain microgreens in indoor crops is a plausible technology that provides nutritionally and phytochemically rich crops.

7.
Clin Chim Acta ; 552: 117695, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38061684

ABSTRACT

BACKGROUND AND AIMS: Cancer predisposition goes beyond BRCA and DNA Mismatch Repair (MMR) genes since multi-gene panel testing has become the routine diagnostic tool for hereditary cancer suspicion (HCS) cases. CHEK2 and PALB2 are some of the foremost-mutated non-BRCA/MMR actionable genes in families with a significant familial aggregation. Therefore, the purpose of this work is to unravel which tumours other than breast, ovary or colorectal display the patients. MATERIALS AND METHODS: We have analysed 528 probands that meet the inclusion criteria for Hereditary Breast and Ovarian Cancer and Lynch Syndrome established by our Hereditary Cancer Regional Program with a customized 35 genes-panel by using Ion Torrent™ Technology. RESULTS: We have identified pathogenic variants (PVs) in 61 families (1.55%), of which more than half (31 probands) harboured PVs in CHEK2 and PALB2 genes. Ours results reveal that not only were PVs CHEK2 and PALB2 carriers more likely to have family history of cancer not limited to breast, ovarian or colorectal cancers, but also they are prone to other extracolonic cancers, noteworthy endometrial and gastric cancers. CONCLUSIONS: Multigene panel testing improves the chance of finding PVs in actionable genes in families with HCS. In addition, the coexistence of variants should be recorded to implement a polygenic risk algorithm that might explain the missing heritability in the aforementioned families.


Subject(s)
Breast Neoplasms , Colorectal Neoplasms , Ovarian Neoplasms , Female , Humans , Germ-Line Mutation/genetics , Genetic Predisposition to Disease , Ovarian Neoplasms/genetics , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Breast Neoplasms/genetics , Genetic Testing/methods , Checkpoint Kinase 2/genetics , Fanconi Anemia Complementation Group N Protein/genetics
8.
Rev Esp Enferm Dig ; 2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38095171

ABSTRACT

The oblique-view echoendoscope is currently the sole tool for ultrasound-guided endoscopic procedures (EUS) in most hospital centers, despite its limitations like a lack of forward vision, issues with needle angle, and restricted accessory device size due to channel angulation. However, our study revealed no significant differences between the oblique and frontal endoscopes, except for minor variations in specific regions. For routine diagnostic studies, interchangeability between the devices is feasible. The anticipated advantages of the frontal device may emerge more prominently in future therapeutic procedures. This suggests that, while the oblique-view echoendoscope remains the primary tool, the frontal device holds potential for evolving roles in diagnostic and therapeutic interventions.

9.
PLoS One ; 18(11): e0293480, 2023.
Article in English | MEDLINE | ID: mdl-37917781

ABSTRACT

This research proposes: (i) analyze push and pull motivations in insular marine protected areas, and (ii) determine their effects on tourists' satisfaction, positive recommendations and loyalty in terms of returning. The study was conducted in the Galápagos Islands in Ecuador; a renowned marine protected area with a National Park being a Natural Heritage Site of Humanity by UNESCO. An exploratory (EFA) and confirmatory factor analysis (CFA), followed by a stepwise multiple regression analysis applied on a sample of 407 tourists in the Galápagos Islands showed four push and pull motivational factors in this destination: "passive marine," "active marine," "novelty and escape," and "social relations". "Passive marine" and "social relations" were the most prominent factors influencing tourist satisfaction and return intentions. Moreover, "passive marine" and "novelty and escape " highly influenced visitors' intention to recommend and give positive feedback about this place. These findings constitute action guides for the adequate management of marine protected areas.


Subject(s)
Intention , Motivation , Ecuador , Personal Satisfaction , Regression Analysis
10.
Rev. Fac. Med. UNAM ; 66(4): 20-25, jul.-ago. 2023. graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1514819

ABSTRACT

Resumen El síndrome de kwashiorkor se caracteriza por malnutrición proteica y edema generalizado; algunos de los factores de riesgo que se asocian a su aparición son: vivir en pobreza, el destete reciente, las infecciones y las dietas basadas en maíz y arroz. Este síndrome puede generar manifestaciones cutáneas como piel delgada y seca, hiperpigmentación, áreas confluentes de descamación, cabello seco, hipopigmentado y desprendible, así como una dermatitis erosiva con predominio en pliegues cutáneos. El diagnóstico se basa principalmente en una evaluación nutricional integral, exploración física y estudios de laboratorio, y el éxito del tratamiento se basa en la rehabilitación nutricional temprana. Caso clínico: lactante del sexo femenino de 8 meses de edad, que acudió al Instituto Nacional de Pediatría (INP), por presentar una dermatosis generalizada de tipo descamativa de 1 mes de evolución, que fue tratada con ketoconazol tópico. Al interrogatorio la madre refiere alimentación exclusiva con atole de maíz por un diagnóstico de "alergia a la leche" y falta de recursos económicos para comprar la fórmula hidrolizada. La paciente presentaba una dermatosis diseminada que afectaba todos los segmentos corporales, caracterizada por placas hiperpigmentadas, bien definidas, de forma irregular, con descamación en láminas gruesas en región perioral y extremidades, así como áreas erosionadas, pálidas y edema generalizado en extremidades. Se realizaron exámenes de laboratorio que mostraron que la paciente tenía anemia (Hb 11.2 g/dL) e hipoalbuminemia (3.3 g/dL) que, en conjunto con las manifestaciones clínicas, integraron el diagnóstico de síndrome de Kwashiorkor. Se informaron los hallazgos clínicos y de laboratorio al servicio de Gastroenterología y Nutrición, quienes realizaron una valoración nutricional integral y decidieron iniciar tratamiento nutricional; por parte del servicio de Dermatología, se indicó el uso de emolientes y cuidados generales de la piel. Veinte días después la dermatosis y el edema habían remitido.


Abstract Kwashiorkor syndrome is characterized by protein malnutrition and edema, risk factors are recent weaning, infections, and diets based on corn and rice. This malnutrition can lead to skin manifestations such as thin, dry skin, hyperpigmentation, confluent areas of scaling, dry, hypopigmented, and detachable hair, as well as erosive dermatitis, predominantly in skin folds. The diagnosis is based on a nutritional evaluation exam, physical examination and laboratory finding, the treatment is based on early nutritional rehabilitation. Clinical case: 8-month-old female infant who attended the Instituto Nacional de Pediatría, presenting a scaling dermatosis of 1 month's evolution that was treated with topical ketoconazole. The mother reported exclusive feeding with corn gruel due to the diagnosis of "lactose allergy" and commented not enough resources to buy hydrolyzed formula. The patient presented a disseminated dermatosis to all body segments, characterized by well-defined, irregularly shaped, hyperpigmented plaques with scaling in thick sheets in the perioral region and extremities, as well as areas of eroded skin and paleness and edema of extremities. Laboratory tests were taken, where anemia (Hb 11.2 g/dl) and hipoalbuminemia (3.3 g/dl) were documented, the diagnosis of kwashiorkor syndrome was integrated. The clinical and laboratory findings were reported to the Gastroenterology and Nutrition service, who performed a nutritional assessment, and began nutritional treatment, emollients and general skin care were documented; twenty days later, the dermatosis and edema had subsided.

11.
Respir Res ; 24(1): 155, 2023 Jun 10.
Article in English | MEDLINE | ID: mdl-37301818

ABSTRACT

BACKGROUND: Diacylglycerol kinase (DGK) regulates intracellular signaling and functions by converting diacylglycerol (DAG) into phosphatidic acid. We previously demonstrated that DGK inhibition attenuates airway smooth muscle (ASM) cell proliferation, however, the mechanisms mediating this effect are not well established. Given the capacity of protein kinase A (PKA) to effect inhibition of ASM cells growth in response to mitogens, we employed multiple molecular and pharmacological approaches to examine the putative role of PKA in the inhibition of mitogen-induced ASM cell proliferation by the small molecular DGK inhibitor I (DGK I). METHODS: We assayed cell proliferation using CyQUANT™ NF assay, protein expression and phosphorylation using immunoblotting, and prostaglandin E2 (PGE2) secretion by ELISA. ASM cells stably expressing GFP or PKI-GFP (PKA inhibitory peptide-GFP chimera) were stimulated with platelet-derived growth factor (PDGF), or PDGF + DGK I, and cell proliferation was assessed. RESULTS: DGK inhibition reduced ASM cell proliferation in cells expressing GFP, but not in cells expressing PKI-GFP. DGK inhibition increased cyclooxygenase II (COXII) expression and PGE2 secretion over time to promote PKA activation as demonstrated by increased phosphorylation of (PKA substrates) VASP and CREB. COXII expression and PKA activation were significantly decreased in cells pre-treated with pan-PKC (Bis I), MEK (U0126), or ERK2 (Vx11e) inhibitors suggesting a role for PKC and ERK in the COXII-PGE2-mediated activation of PKA signaling by DGK inhibition. CONCLUSIONS: Our study provides insight into the molecular pathway (DAG-PKC/ERK-COXII-PGE2-PKA) regulated by DGK in ASM cells and identifies DGK as a potential therapeutic target for mitigating ASM cell proliferation that contributes to airway remodeling in asthma.


Subject(s)
Cyclic AMP-Dependent Protein Kinases , Diacylglycerol Kinase , Diacylglycerol Kinase/metabolism , Diacylglycerol Kinase/pharmacology , Cyclic AMP-Dependent Protein Kinases/metabolism , Cyclic AMP-Dependent Protein Kinases/pharmacology , Cells, Cultured , Cell Proliferation , Myocytes, Smooth Muscle/metabolism
13.
Res Dev Disabil ; 136: 104467, 2023 May.
Article in English | MEDLINE | ID: mdl-36905781

ABSTRACT

BACKGROUND: Emotional competencies are skills necessary to adequately understand, express, and regulate emotional phenomena. Among the emotional competencies is emotion regulation. Not having adequate development of this emotional competence is related to psychological problems such as depression. One of the characteristics of individuals with developmental disabilities is the presence of difficulties with emotion regulation. These difficulties can affect an individual's autonomy, social competence, and the development of independent life. AIMS: This paper presents a scoping review to identify the technology designed and developed to support the emotion regulation of individuals with developmental disabilities. METHODS AND PROCEDURES: We combined the guidelines for a systematic literature review in computer science and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. The process resulted in twelve stages through which we conducted this scoping review. First, a search query was defined and executed in computer science's five most representative search engines. We used different inclusion, exclusion, and quality criteria for selecting the works included in this review. OUTCOMES AND RESULTS: Thirty-nine papers aimed at supporting the emotional competencies of individuals with developmental disabilities were included, of which nine support emotion regulation. As a result, different areas of opportunity in developing technology to support the emotion regulation of individuals with developmental disabilities are discussed. CONCLUSIONS AND IMPLICATIONS: Technology supporting emotion regulation in individuals with developmental disabilities is a growing but little-explored field. For the literature supporting emotion regulation, we detected opportunities for study. Some of them aimed at investigating whether we could use technologies developed for other emotional competencies to support emotion regulation and how the characteristics of this technology can support individuals with developmental disabilities.


Subject(s)
Emotional Regulation , Child , Humans , Developmental Disabilities/psychology
15.
Heliyon ; 8(10): e10867, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36211999

ABSTRACT

The COVID-19 pandemic has prompted the re-emergence of staycations to the fore, as many people were forced to spend their vacations at or close to home due to travel restrictions. This phenomenon first went mainstream during the 2008 financial crisis, and has now been further accelerated by the COVID-19 pandemic. This study investigated the growth and practice of staycations during the first two years of the pandemic by analyzing social media and internet search data using Latent Dirichlet Allocation (LDA) topic modeling and Google Trends analytics. Key findings suggest that, while spatially close to home, people tried to achieve a psychological distance away from home. This was demonstrated by a strong global search interest in spending staycations at hotels close to home. The optimal LDA topic model produced 38 topics which were classified under four aggregate dimensions of antecedents, attributes, activities, and consequences of staycations. The findings provide useful insights to managers and policymakers on boosting revenue through this practice, and the role of staycations in promoting leisure activities close to home and sustainable tourism.

16.
Int J Mol Sci ; 23(19)2022 Oct 06.
Article in English | MEDLINE | ID: mdl-36233170

ABSTRACT

Airway remodeling in asthma involves the hyperproliferation of airway smooth muscle (ASM) cells. However, the molecular signals that regulate ASM growth are not completely understood. Gq-coupled G protein-coupled receptor and receptor tyrosine kinase signaling regulate ASM cell proliferation via activation of phospholipase C, generation of inositol triphosphate (IP3) and diacylglycerol (DAG). Diacylglycerol kinase (DGK) converts DAG into phosphatidic acid (PA) and terminates DAG signaling while promoting PA-mediated signaling and function. Herein, we hypothesized that PA is a pro-mitogenic second messenger in ASM, and DGK inhibition reduces the conversion of DAG into PA resulting in inhibition of ASM cell proliferation. We assessed the effect of pharmacological inhibition of DGK on pro-mitogenic signaling and proliferation in primary human ASM cells. Pretreatment with DGK inhibitor I (DGKI) significantly inhibited platelet-derived growth factor-stimulated ASM cell proliferation. Anti-mitogenic effect of DGKI was associated with decreased mTOR signaling and expression of cyclin D1. Exogenous PA promoted pro-mitogenic signaling and rescued DGKI-induced attenuation of ASM cell proliferation. Finally, house dust mite (HDM) challenge in wild type mice promoted airway remodeling features, which were attenuated in DGKζ-/- mice. We propose that DGK serves as a potential drug target for mitigating airway remodeling in asthma.


Subject(s)
Airway Remodeling , Asthma , Animals , Asthma/metabolism , Cell Proliferation , Cyclin D1/metabolism , Diacylglycerol Kinase/genetics , Diacylglycerol Kinase/metabolism , Diglycerides/metabolism , Humans , Inositol/pharmacology , Mice , Mitogens/pharmacology , Myocytes, Smooth Muscle/metabolism , Phosphatidic Acids/metabolism , Platelet-Derived Growth Factor/metabolism , Platelet-Derived Growth Factor/pharmacology , Protein-Tyrosine Kinases/metabolism , Receptors, G-Protein-Coupled/metabolism , TOR Serine-Threonine Kinases/metabolism , Type C Phospholipases/metabolism
17.
Int J Mol Sci ; 23(19)2022 Sep 29.
Article in English | MEDLINE | ID: mdl-36232793

ABSTRACT

The probability of carrying two pathogenic variants (PVs) in dominant cancer-predisposing genes for hereditary breast and ovarian cancer and lynch syndromes in the same patient is uncommon, except in populations where founder effects exist. Two breast cancer women that are double heterozygotes (DH) for both BRCA1/BRCA2, one ovarian cancer case DH for BRCA1/RAD51C, and another breast and colorectal cancer who is DH for BRCA2/PMS2 were identified in our cohort. Ages at diagnosis and severity of disease in BRCA1/BRCA2 DH resembled BRCA1 single-carrier features. Similarly, the co-existence of the BRCA2 and PMS2 mutations prompted the development of breast and colorectal cancer in the same patient. The first BRCA1/BRCA2 DH was identified by HA-based and Sanger sequencing (1 of 623 families with BRCA PVs). However, this ratio has increased up to 2.9% (1 DH carrier vs. 103 single PV carriers) since using a custom 35-cancer gene on-demand panel. The type of cancer developed in each DH patient was consistent with the independently inherited condition, and the clinical outcome was no worse than in patients with single BRCA1 mutations. Therefore, the clinical impact, especially in patients with two hereditary syndromes, lies in genetic counseling tailor-made for each family based on the clinical guidelines for each syndrome. The number of DH is expected to be increased in the future as a result of next generation sequencing routines.


Subject(s)
Breast Neoplasms , Colorectal Neoplasms, Hereditary Nonpolyposis , Ovarian Neoplasms , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Carcinoma, Ovarian Epithelial/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Female , Genes, BRCA2 , Genetic Predisposition to Disease , Genetic Testing , Humans , Mismatch Repair Endonuclease PMS2/genetics , Mutation , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/genetics
18.
Crit Care Nurs Clin North Am ; 34(2): 151-156, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35660228

ABSTRACT

Guideline-directed medical treatment (GDMT) is the mainstay of treatment for patients with heart failure (HF). Despite compelling evidence, patient and provider adherence to these guidelines remains low. This is mostly due to the complexity of the GDMT regimen and the competing comorbid conditions. The COVID-19 pandemic has further complicated the initiation and maintenance of GDMT and overall care for patients with HF. Telemedicine will erase many of the barriers to appropriate HF care that were present before, during, and long after the COVID-19 pandemic has ended.


Subject(s)
COVID-19 , Heart Failure , Telemedicine , Heart Failure/drug therapy , Humans , Pandemics , Stroke Volume
19.
Malar J ; 21(1): 148, 2022 May 15.
Article in English | MEDLINE | ID: mdl-35570274

ABSTRACT

BACKGROUND: Species of Plasmodium (Haemosporida, Plasmodiidae) are remarkably diverse haemoparasites. Information on genetic diversity of avian malaria pathogens has been accumulating rapidly, however exo-erythrocytic development of these organisms remains insufficiently addressed. This is unfortunate because, contrary to Plasmodium species parasitizing mammals, the avian malaria parasites undergo several cycles of exo-erythrocytic development, often resulting in damage of various organs. Insufficient knowledge on the exo-erythrocytic development in most described Plasmodium species precludes the understanding of mechanisms of virulence during avian malaria. This study extends information on the exo-erythrocytic development of bird malaria parasites. METHODS: A roadkill fieldfare (Turdus pilaris) was sampled in Switzerland and examined using pathologic, cytologic, histologic, molecular and microbiologic methods. Avian malaria was diagnosed, and erythrocytic and exo-erythrocytic stages of the parasite were identified using morphologic characteristics and barcode DNA sequences of the cytochrome b gene. The species-specific characteristics were described, illustrated, and pathologic changes were reported. RESULTS: An infection with Plasmodium matutinum lineage pLINN1 was detected. Parasitaemia was relatively low (0.3%), with all erythrocytic stages (trophozoites, meronts and gametocytes) present in blood films. Most growing erythrocytic meronts were markedly vacuolated, which is a species-specific feature of this parasite's development. Phanerozoites at different stages of maturation were seen in leukocytes, macrophages, and capillary endothelial cells in most organs examined; they were particularly numerous in the brain. Like the erythrocytic meronts, growing phanerozoites were markedly vacuolated. Conspicuous exo-erythrocytic development and maturation in leucocytes suggests that this fieldfare was not adapted to the infection and the parasite was capable to escape from cellular immunity. CONCLUSIONS: This is the first report of exo-erythrocytic development of the malaria parasite lineage pLINN1 during single infection and the first report of this lineage in the fieldfare. The findings of multiple phanerozoites in brain, skeletal muscle, and eye tissue in combination with signs of vascular blockage and thrombus formation strongly suggest an impaired vision and neuromuscular responsiveness as cause of the unexpected collision with a slowly moving car. Further studies on exo-erythrocytic stages of haemosporidian parasites are pivotal to understand the true level of populational damage of avian malaria in wild birds.


Subject(s)
Haemosporida , Malaria, Avian , Plasmodium , Songbirds , Animals , Endothelial Cells , Haemosporida/physiology , Malaria, Avian/parasitology , Mammals , Phylogeny , Plasmodium/physiology , Songbirds/parasitology
20.
VideoGIE ; 7(3): 102-105, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35287367

ABSTRACT

Video 1Endoscopically directed single-port intragastric procedures in a porcine model.

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