Introduction
Intranodal palisaded myofibroblastoma (IPM) is an exceedingly rare benign mesenchymal tumor of the lymph nodes. Magnetic resonance imaging (MRI) findings are unspecific, which may ...present diagnostic challenges to fine‐needle aspiration cytology (FNAC). The histological and immunohistochemical features of IPM are unique.
Case Report
A previously healthy 40‐year‐old male patient presented a slow‐growing solitary left inguinal mass. FNAC revealed clustered cells within a metachromatic stroma, single spindle cells without atypia, hemosiderin pigment, and siderophages. An MRI showed a central hyperintense septum in fat‐suppressed, T2‐weighted sequences. The excised lymph node contained central haphazard fascicles of spindle cells with focal nuclear palisading, hemosiderin pigment, extravasated erythrocytes, and hemorrhagic areas. Vimentin and smooth muscle actin were diffusely positive. Amianthoid collagen fibers were not clearly observed.
Conclusion
IPM is an extremely rare mesenchymal benign intranodal tumor that should be included in the differential diagnosis of spindle cell lesions in the inguinal region.
Obesity-induced hypogonadism (OIH) is a prevalent, but often neglected condition in men, which aggravates the metabolic complications of overweight. While hypothalamic suppression of Kiss1-encoded ...kisspeptin has been suggested to contribute to OIH, the molecular mechanisms for such repression in obesity, and the therapeutic implications thereof, remain unknown.
A combination of bioinformatic, expression and functional analyses was implemented, assessing the role of the evolutionary-conserved miRNAs, miR-137 and miR-325, in mediating obesity-induced suppression of hypothalamic kisspeptin, as putative mechanism of central hypogonadism and metabolic comorbidities. The implications of such miR-137/325-kisspeptin interplay for therapeutic intervention in obesity were also explored using preclinical OIH models.
MiR-137/325 repressed human KISS1 3’-UTR in-vitro and inhibited hypothalamic kisspeptin content in male rats, while miR-137/325 expression was up-regulated, and Kiss1/kisspeptin decreased, in the medio-basal hypothalamus of obese rats. Selective over-expression of miR-137 in Kiss1 neurons reduced Kiss1/ kisspeptin and partially replicated reproductive and metabolic alterations of OIH in lean mice. Conversely, interference of the repressive actions of miR-137/325 selectively on Kiss1 3’-UTR in vivo, using target-site blockers (TSB), enhanced kisspeptin content and reversed central hypogonadism in obese rats, together with improvement of glucose intolerance, insulin resistance and cardiovascular and inflammatory markers, despite persistent exposure to obesogenic diet. Reversal of OIH by TSB miR-137/325 was more effective than chronic kisspeptin or testosterone treatments in obese rats.
Our data disclose that the miR-137/325-Kisspeptin repressive interaction is a major player in the pathogenesis of obesity-induced hypogonadism and a putative druggable target for improved management of this condition and its metabolic comorbidities in men suffering obesity.
Up to half of the men suffering obesity display also central hypogonadism, an often neglected complication of overweight that can aggravate the clinical course of obesity and its complications. The mechanisms for such obesity-induced hypogonadism remain poorly defined. We show here that the evolutionary conserved miR137/miR325 tandem centrally mediates obesity-induced hypogonadism via repression of the reproductive-stimulatory signal, kisspeptin; this may represent an amenable druggable target for improved management of hypogonadism and other metabolic complications of obesity.
•Central hypogonadism is a prevalent condition in men with obesity, of as yet unknown mechanisms•Long-term obesity has been suggested to suppress Kiss1 neurons in the ARC of male rodents, via ill-defined molecular mechanisms•Hypothalamic miR-137/miR-325 are upregulated in obese male rats and repress Kiss1/kisspeptin•Blockade of this repressive interaction reverses central hypogonadism and metabolic comorbidities•This reversal is more effective than those induced by treatments with testosterone or kisspeptin
The prohibitin (PHB)-binding compound fluorizoline as well as PHB-downregulation activate the integrated stress response (ISR) in HEK293T and U2OS human cell lines. This activation is denoted by ...phosphorylation of eIF2α and increases in ATF4, ATF3, and CHOP protein levels. The blockage of the activation of the ISR by overexpression of GRP78, as well as an increase in IRE1 activity, indicate the presence of ER stress after fluorizoline treatment. The inhibition of the ER stress response in HEK293T and U2OS led to increased sensitivity to fluorizoline-induced apoptosis, indicating a pro-survival role of this pathway after fluorizoline treatment in these cell lines. Fluorizoline induced an increase in calcium concentration in the cytosol and the mitochondria. Finally, two different calcium chelators reduced fluorizoline-induced apoptosis in U2OS cells. Thus, we have found that fluorizoline causes increased ER stress and activation of the integrated stress response, which in HEK293T and U2OS cells are protective against fluorizoline-induced apoptosis.
The effect of high-flow oxygen therapy vs conventional oxygen therapy has not been established in the setting of severe COVID-19.
To determine the effect of high-flow oxygen therapy through a nasal ...cannula compared with conventional oxygen therapy on need for endotracheal intubation and clinical recovery in severe COVID-19.
Randomized, open-label clinical trial conducted in emergency and intensive care units in 3 hospitals in Colombia. A total of 220 adults with respiratory distress and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of less than 200 due to COVID-19 were randomized from August 2020 to January 2021, with last follow-up on February 10, 2021.
Patients were randomly assigned to receive high-flow oxygen through a nasal cannula (n = 109) or conventional oxygen therapy (n = 111).
The co-primary outcomes were need for intubation and time to clinical recovery until day 28 as assessed by a 7-category ordinal scale (range, 1-7, with higher scores indicating a worse condition). Effects of treatments were calculated with a Cox proportional hazards model adjusted for hypoxemia severity, age, and comorbidities.
Among 220 randomized patients, 199 were included in the analysis (median age, 60 years; n = 65 women 32.7%). Intubation occurred in 34 (34.3%) randomized to high-flow oxygen therapy and in 51 (51.0%) randomized to conventional oxygen therapy (hazard ratio, 0.62; 95% CI, 0.39-0.96; P = .03). The median time to clinical recovery within 28 days was 11 (IQR, 9-14) days in patients randomized to high-flow oxygen therapy vs 14 (IQR, 11-19) days in those randomized to conventional oxygen therapy (hazard ratio, 1.39; 95% CI, 1.00-1.92; P = .047). Suspected bacterial pneumonia occurred in 13 patients (13.1%) randomized to high-flow oxygen and in 17 (17.0%) of those randomized to conventional oxygen therapy, while bacteremia was detected in 7 (7.1%) vs 11 (11.0%), respectively.
Among patients with severe COVID-19, use of high-flow oxygen through a nasal cannula significantly decreased need for mechanical ventilation support and time to clinical recovery compared with conventional low-flow oxygen therapy.
ClinicalTrials.gov Identifier: NCT04609462.
Abstract Background Developing, testing and implementing evidence-based prevention interventions are important in decreasing substance use and sexual risk behavior among adolescents. This process ...requires research expertise, infrastructure, resources and decades of research testing, which might not always be feasible for low resource countries. Adapting and testing interventions proven to be efficacious in similar cultures might circumvent the time and costs of implementing evidence-based interventions in new settings. This paper describes the two-phase study, including training and development of the research infrastructure in the Ecuadorian university necessary to implement a randomized controlled trial. Methods/design Familias Unidas is a multilevel parent-centered intervention designed in the U.S. to prevent drug use and sexual risk behaviors in Hispanic adolescents. The current study consisted of Phase 1 feasibility study (n = 38) which adapted the intervention and study procedures within a single-site school setting in an area with a high prevalence of drug use and unprotected sexual behavior among adolescents in Ecuador, and Phase 2 randomized controlled trial of the adapted intervention in two public high schools with a target population of families with adolescents from 12 to 14 years old. Discussion The trial is currently in Phase 2. Study recruitment was completed with 239 parent-youth dyads enrolling. The intervention phase and the first follow-up assessment have been completed. The second and third follow-up assessments will be completed in 2016. This project has the potential of benefitting a large population of families in areas of Ecuador that are disproportionally affected by drug trafficking and its consequences. Trial registration MSP-DIS-2015-0055-0, Ministry of Public Health (MSP), Quito, Ecuador.
To prospectively evaluate the validity of a PCR assay in CSF for the diagnosis of neurocysticercosis (NC).
We conducted a multicenter, prospective case-control study, recruiting participants from 5 ...hospitals in Cuenca, Ecuador, from January 2015 to February 2016. Cases fulfilled validated diagnostic criteria for NC. For each case, a neurosurgical patient who did not fulfill the diagnostic criteria for NC was selected as a control. CT and MRI, as well as a CSF sample, were collected from both cases and controls. The diagnostic criteria to identify cases were used as a reference standard.
Overall, 36 case and 36 control participants were enrolled. PCR had a sensitivity of 72.2% (95% confidence interval CI 54.8%-85.8%) and a specificity of 100.0% (95% CI 90.3%-100.0%). For parenchymal NC, PCR had a sensitivity of 42.9% (95% CI 17.7%-71.1%), and for extraparenchymal NC, PCR had a sensitivity of 90.9% (95% CI 70.8%-98.9%).
This study demonstrated the usefulness of this PCR assay in CSF for the diagnosis of NC. PCR may be particularly helpful for diagnosing extraparenchymal NC when neuroimaging techniques have failed.
This study provides Class III evidence that CSF PCR can accurately identify patients with extraparenchymal NC.
Trichosporonosis is an opportunistic infection caused by the genus Trichosporon. The majority of cases of invasive trichosporonosis occurs in immunocompromised individuals.
We describe a case of ...disseminated infection by Trichosporon asahii in a hematology patient. A 52-year-old man diagnosed with acute lymphoblastic leukemia developed a febrile episode during the third cycle of the induction chemotherapy. The blood cultures were positive after 24h incubation, showing elongated structures compatible with fungal elements in the Gram stain. The identification of the fungus as Trichosporon asahii was carried out by the assimilation of compounds of carbon and the amplification and sequencing of the D1/D2 domain and the internal transcribed spacer of the ribosomal DNA. The fungus was also isolated from the pustular lesions that the patient had in the chest. After treatment with amphotericin B, the patient progressed satisfactorily.
Trichosporon asahii is an emergent pathogen in immunosupressed patients and its presence should not be considered as colonization, as there is risk of invasive infection.
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