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1.
Dig Dis Sci ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977524

RESUMO

BACKGROUND: Virtual interviews are still recommended for fellowship applications, 3 years after the beginning of the COVID-19 pandemic. Improving equity by reducing the cost for the applicants has been the most important reason for continuing virtual interviews. However, some argue that important information may be missed in a virtual setting. Our objective was to assess the perspective of Gastroenterology (GI) fellowship interviewers and applicants toward virtual interviews. METHODS: We designed two different anonymous surveys directed at GI programs and GI applicants who were interviewed for GI fellowship programs from 2020 to 2022 and matched to a GI program. Survey links were emailed to the Program Directors (PDs) and Program Coordinators via the AGA listserv starting in January 2023. A descriptive analysis was performed using Excel, and Fisher's exact tests were performed using R version 4.3.1. RESULTS: Sixty-one applicants and 79 interviewers responded to our survey. More than 80% of applicants strongly agreed (n = 36; 59%) and agreed (n = 14; 23%) that they would prefer in-person interviews if money was not an issue. When applicants were asked about the interview format in order of their preference, "in-person, hybrid, virtual" was the most popular answer (n = 16; 26.2%). Most interviewers (n = 47; 59.5%) do not prefer virtual interviews over in-person interviews. Furthermore, some interviewers were rarely able to judge the applicants' interpersonal (n = 17; 21.5%) and ethical skills (n = 16; 20.3%). These results differed according to the type of interviewer (p = 0.013 and 0.018, respectively). CONCLUSION: Based on our survey, most programs still prefer in-person interviews. Despite the several advantages of virtual interviews, the majority of applicants would prefer an in-person setting if the financial burden was not a factor. Nonetheless, many applicants think that the cost savings outweigh all the disadvantages associated with virtual interviews. The lack of empathy, personal connections, and engagement may impact the ability of interviewers to judge and ultimately rank a candidate. The virtual interview is here to stay, and we need input from the applicants and the interviewers to make the process more productive.

2.
Cancer Invest ; : 1-11, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007916

RESUMO

Limited research has compared cognition of people with non-central nervous system metastatic cancer (NCM) vs. metastatic brain cancer (BM). This prospective cross-sectional study was comprised 37 healthy controls (HC), 40 NCM, and 61 BM completing 10 neuropsychological tests. The NCM performed below HCs on processing speed and executive functioning tasks, while the BM group demonstrated lower performance across tests. Tasks of processing speed, verbal fluency, and verbal memory differentiated the clinical groups (BM < NCM). Nearly 20% of the NCM group was impaired on at least three neuropsychological tests whereas approximately 40% of the BM group demonstrated the same level of impairment.

3.
Shock ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39012765

RESUMO

ABSTRACT: Both abdominal radiotherapy and a nuclear event can result in gastrointestinal symptoms, including acute radiation syndrome (GI-ARS). GI-ARS is characterized by compromised intestinal barrier integrity increasing the risk for infectious complications. Physiologically relevant animal models are crucial for elucidating host responses and therapeutic targets. We aimed to determine the radiation dose requirements for creating GI-ARS in the Sinclair minipig. Male, sexually mature swine were randomly divided into sham (n = 6) and three lower hemibody radiation dosage groups of 8, 10, and 12 Gy (n = 5/group) delivered using a linear accelerator-derived X-rays (1.9 Gy/min). Animals were monitored for GI-ARS symptoms for 14 days with rectal swab and blood collection at days 0-3, 7, 10, and 14 followed by necropsy for western blotting and histology. Dose-dependent increases in weight loss, diarrhea severity, and mortality (log-rank test, p = 0.041) were seen. Villi length was significantly reduced in all irradiated animals compared to controls (p < 0.001). Serum citrulline decreased and bacterial translocation increased post-irradiation compared to controls. Increased NLRP3 levels in post-mortem jejunum were seen (p = 0.0043) as well as increased IL-1ß levels in the 12 Gy group (p = 0.041). Radiation dose and survival were associated with significant gut microbial community shifts in beta diversity. Moreover, decedents had increased Porphyromonas, Campylobacter, Bacteroides, Parvimonas, and decreased Fusobacterium and decreased Aerococcus, Lactobacillus, Prevotella, and Streptococcus. Our novel Sinclair minipig model showed dose-dependent clinical symptoms of GI-ARS. These findings provide invaluable insights into the intricate interplay between GI-ARS, intestinal inflammation, and gut microbiota alterations offering potential targets for therapeutic and diagnostic interventions after radiation exposure.

4.
J Gene Med ; 26(7): e3717, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38967915

RESUMO

BACKGROUND: Synaptic Ras GTPase activating protein 1 (SYNGAP1)-related non-specific intellectual disability is a neurodevelopmental disorder caused by an insufficient level of SynGAP1 resulting in a dysfunction of neuronal synapses and presenting with a wide array of clinical phenotypes. Hematopoietic stem cell gene therapy has the potential to deliver therapeutic levels of functional SynGAP1 to affected neurons upon transduction of hematopoietic stem and progenitor cells with a lentiviral vector. METHODS: As a novel approach toward the treatment of SYNGAP1, we have generated a lentiviral vector expressing a modified form of SynGAP1 for transduction of human CD34+ hematopoietic stem and progenitor cells. The gene-modified cells were then transplanted into adult immunodeficient SYNGAP1+/- heterozygous mice and evaluated for improvement of SYNGAP1-related clinical phenotypes. Expression of SynGAP1 was also evaluated in the brain tissue of transplanted mice. RESULTS: In our proof-of-concept study, we have demonstrated significant improvement of SYNGAP1-related phenotypes including an improvement in motor abilities observed in mice transplanted with the vector transduced cells because they displayed decreased hyperactivity in an open field assay and an increased latency to fall in a rotarod assay. An increased level of SynGAP1 was also detected in the brains of these mice. CONCLUSIONS: These early-stage results highlight the potential of this stem cell gene therapy approach as a treatment strategy for SYNGAP1.


Assuntos
Terapia Genética , Vetores Genéticos , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Deficiência Intelectual , Lentivirus , Proteínas Ativadoras de ras GTPase , Animais , Proteínas Ativadoras de ras GTPase/genética , Proteínas Ativadoras de ras GTPase/metabolismo , Terapia Genética/métodos , Humanos , Células-Tronco Hematopoéticas/metabolismo , Camundongos , Deficiência Intelectual/terapia , Deficiência Intelectual/genética , Vetores Genéticos/genética , Lentivirus/genética , Transdução Genética , Modelos Animais de Doenças , Encéfalo/metabolismo
5.
Anesthesiology ; 140(6): 1088-1097, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38629957

RESUMO

BACKGROUND: Colorectal cancer is a leading cause of cancer-related death. Adenomas and serrated polyps are precursors of colorectal cancer, with serrated polyps being more difficult to detect during colonoscopy. The relationship between propofol use and polyp detection remains unclear. The authors investigated the association of propofol-based versus mild-moderate sedation on adenoma and serrated polyp detection during colonoscopy. METHODS: This retrospective cohort study used observational data from the New Hampshire Colonoscopy Registry. Patients aged greater than 50 yr with screening or surveillance colonoscopies between January 1, 2015, and February 28, 2020, were included. Exclusions were diagnostic examinations, no sedation, missing pathology data, and poor bowel preparation. Multivariate logistic regression was used to evaluate differences in polyp detection between propofol and moderate sedation in the full sample while adjusting for covariates. Propensity score adjustment and clustering at the endoscopist level were used in a restricted sample analysis that included endoscopists and facilities with between 5% and 95% propofol sedation use. RESULTS: A total of 54,063 colonoscopies were analyzed in the full sample and 18,998 in the restricted sample. Serrated polyp prevalence was significantly higher using propofol (9,957 of 29,312; 34.0% [95% CI, 33.4 to 34.5%]) versus moderate sedation (6,066 of 24,751; 24.5% [95% CI, 24.0 to 25.1%]) in the full sample and restricted samples (1,410 of 4,661; 30.3% [95% CI, 28.9 to 31.6%] vs. 3,690 of 14,337; 25.7% [95% CI, 25.0 to 26.5%]). In the full sample multivariate logistic regression, propofol was associated with higher neoplasm (adjusted odds ratio, 1.25 [95% CI, 1.21 to 1.29]), adenoma (odds ratio, 1.07 [95% CI, 1.03 to 1.11]), and serrated polyp detection (odds ratio, 1.51 [95% CI, 1.46 to 1.57]). In the restricted sample using inverse probability of treatment weighted propensity score adjustment and clustering at the endoscopist level, an attenuated but statistically significant effect size was observed for serrated polyps (odds ratio, 1.13 [95% CI, 1.07 to 1.19]), but not for adenomas (odds ratio, 1.00 [95% CI, 0.95 to 1.05]) or any neoplastic lesion (odds ratio, 1.03 [95% CI, 0.98 to 1.08]). CONCLUSIONS: Propofol sedation during colonoscopy may be associated with improved detection of serrated polyps, but not adenomas.


Assuntos
Pólipos do Colo , Colonoscopia , Propofol , Sistema de Registros , Humanos , Colonoscopia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Pólipos do Colo/diagnóstico , Pólipos do Colo/epidemiologia , Estudos Retrospectivos , Propofol/administração & dosagem , Idoso , Estudos de Coortes , Hipnóticos e Sedativos/administração & dosagem , Sedação Consciente/métodos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/diagnóstico
6.
Int J Mol Sci ; 25(8)2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38674120

RESUMO

Hematopoietic acute radiation syndrome (H-ARS) involves injury to multiple organ systems following total body irradiation (TBI). Our laboratory demonstrated that captopril, an angiotensin-converting enzyme inhibitor, mitigates H-ARS in Göttingen minipigs, with improved survival and hematopoietic recovery, as well as the suppression of acute inflammation. However, the effects of captopril on the gastrointestinal (GI) system after TBI are not well known. We used a Göttingen minipig H-ARS model to investigate captopril's effects on the GI following TBI (60Co 1.79 or 1.80 Gy, 0.42-0.48 Gy/min), with endpoints at 6 or 35 days. The vehicle or captopril (0.96 mg/kg) was administered orally twice daily for 12 days, starting 4 h post-irradiation. Ilea were harvested for histological, protein, and RNA analyses. TBI increased congestion and mucosa erosion and hemorrhage, which were modulated by captopril. GPX-4 and SLC7A11 were downregulated post-irradiation, consistent with ferroptosis at 6 and 35 days post-irradiation in all groups. Interestingly, p21/waf1 increased at 6 days in vehicle-treated but not captopril-treated animals. An RT-qPCR analysis showed that radiation increased the gene expression of inflammatory cytokines IL1B, TNFA, CCL2, IL18, and CXCL8, and the inflammasome component NLRP3. Captopril suppressed radiation-induced IL1B and TNFA. Rectal microbiome analysis showed that 1 day of captopril treatment with radiation decreased overall diversity, with increased Proteobacteria phyla and Escherichia genera. By 6 days, captopril increased the relative abundance of Enterococcus, previously associated with improved H-ARS survival in mice. Our data suggest that captopril mitigates senescence, some inflammation, and microbiome alterations, but not ferroptosis markers in the intestine following TBI.


Assuntos
Síndrome Aguda da Radiação , Captopril , Modelos Animais de Doenças , Ferroptose , Microbioma Gastrointestinal , Inflamação , Porco Miniatura , Irradiação Corporal Total , Animais , Síndrome Aguda da Radiação/tratamento farmacológico , Suínos , Inflamação/patologia , Captopril/farmacologia , Irradiação Corporal Total/efeitos adversos , Ferroptose/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/microbiologia , Intestinos/patologia , Intestinos/efeitos dos fármacos , Intestinos/efeitos da radiação , Masculino , Inibidores da Enzima Conversora de Angiotensina/farmacologia
8.
Am J Gastroenterol ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38629701

RESUMO

INTRODUCTION: Negative colonoscopies following positive stool tests could result from stool test characteristics or from the quality of endoscopist performance. We used New Hampshire Colonoscopy Registry data to examine the association between endoscopist detection rates and polyp yield in colonoscopies performed for positive fecal immunochemical test (FIT) or multitarget stool DNA (mt-sDNA) test to evaluate the degree to which positive stool tests followed by negative colonoscopy ("false positives") vary with endoscopist quality. In addition, we investigated the frequency of significant polyps in the subgroup of highest quality colonoscopies following positive stool tests. METHODS: We compared the frequencies of negative colonoscopies and of specific polyps following positive stool tests across quartiles of endoscopist adenoma detection rate (ADR) and clinically significant serrated polyp detection rate (CSSDR). RESULTS: Our sample included 864 mt-sDNA+ and 497 FIT+ patients. We found a significantly lower frequency of negative colonoscopies following positive stool tests among endoscopists with higher ADR and CSSDR, particularly in the 2 highest quartiles. In addition, detection of any adenoma after a positive stool test for endoscopists in the fourth ADR quartile was 63.3% (FIT+) and 62.8% (mt-sDNA+). Among endoscopists in the fourth CSSDR quartile, sessile serrated lesions were found in 29.2% of examinations following a positive mt-sDNA and in 13.5% following FIT+ examinations. DISCUSSION: The frequency of negative colonoscopies after positive stool tests was significantly higher in examinations performed by endoscopists with low ADR and CSSDR. Our results also suggest a benchmark target of at least 40% for ADR in patients with mt-sDNA+ or FIT+ tests and 20% for sessile serrated lesions in mt-sDNA+ patients.

9.
Aliment Pharmacol Ther ; 59(9): 1033-1048, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38534182

RESUMO

BACKGROUND: The faecal immunochemical test (FIT) is an inexpensive and convenient modality to screen for colorectal cancer. However, its one-time sensitivity for detecting colorectal cancer and cancer precursors is limited. There is growing interest in using the non-haemoglobin contents of FIT residual buffer to enhance colonic neoplasia detection. AIM: To establish from the literature a framework to catalogue candidate biomarkers within FIT residual buffer for non-invasive colorectal cancer screening. METHODS: The search strategy evaluated PubMed, Scopus, Web of Science, Embase, and Google Scholar for publications through 25 October 2023, with search terms including FIT, buffer, OC-sensor, biomarkers, microbiome, microRNA (miR), colon, rectum, screening, neoplasm, and early detection. Studies employing home-based collection samples using quantitative FIT first processed for haemoglobin were included. One author reviewed all articles; a second author completed a 20% full-text audit to ensure adherence to eligibility criteria. RESULTS: A broad search yielded 1669 studies and application of eligibility criteria identified 18 relevant studies. Multiple protein, DNA/RNA, and microbiome biomarkers (notably haptoglobin, miR-16, miR-27a-3p, miR-92a, miR-148a-3p, miR-223, miR-421, let-7b-5p, and Tyzzerella 4) were associated with colorectal neoplasia. Furthermore, studies highlighted the short-term stability of biomarkers for clinical use and long-term stability for research purposes. CONCLUSIONS: This scoping review summarises the framework and progress of research on stability of biomarkers in FIT residual buffer and their associations with colorectal neoplasia to guide opportunities for further confirmatory studies to enhance colorectal cancer screening.


Assuntos
Neoplasias Colorretais , MicroRNAs , Humanos , Detecção Precoce de Câncer , Neoplasias Colorretais/diagnóstico , Reto , Hemoglobinas/metabolismo , Sangue Oculto , Biomarcadores/análise , Fezes/química , Programas de Rastreamento
10.
Cureus ; 16(1): e53234, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38425591

RESUMO

A chondrosarcoma with pulmonary metastatic calcifications is a rarely reported phenomenon. This report discusses chondrosarcomas and their clinical features, diagnosis, and treatment, using as an example the case of a 55-year-old female with a right pelvic chondrosarcoma that developed over 10 years. In the last two years, the patient had increasing pulmonary findings, including pulmonary nodules, ground glass opacities, and likely pulmonary metastatic calcifications. The objective of this report is to explore chondrosarcomas and their pattern of metastatic presentation, with the hope of improving recognition of the disease and streamlining treatment.

11.
Bone ; 181: 117029, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38331307

RESUMO

Blast-related traumatic heterotopic ossification (tHO) impacts clinical outcomes in combat-injured patients, leading to delayed wound healing, inflammatory complications, and reduced quality of life. Blast injured patients often have significant burns. This study investigated whether a partial thickness thermal burn injury exacerbates blast-related tHO in a clinically relevant polytrauma animal model. Adult male Sprague Dawley rats were subjected to an established model involving a whole-body blast overpressure exposure (BOP), complex extremity trauma followed by hind limb amputation (CET) followed by the addition of a 10 % total body surface area (TBSA) second degree thermal burn (BU). Micro-CT scans on post-operative day 56 showed a significant increase in HO volume in the CET + BU as compared to the CET alone injury group (p < .0001; 22.83 ± 3.41 mm3 vs 4.84 ± 5.77 mm3). Additionally, CET + BU concomitant with BOP significantly increased HO (p < .0001; 34.95 ± 7.71 mm3) as compared to CET + BU alone, confirming BOP has a further synergistic effect. No HO was detectable in rats in the absence of CET. Serum analysis revealed similar significant elevated (p < .0001) levels of pro-inflammatory markers (Cxcl1 and Il6) at 6 h post-injury (hpi) in the CET + BU and BOP + CET + BU injury groups as compared to naïve baseline values. Real-time qPCR demonstrated similar levels of chondrogenic and osteogenic gene expression in muscle tissue at the site of injury at 168 hpi in both the CET + BU and BOP+CET + BU injury groups. These results support the hypothesis that a 10 % TBSA thermal burn markedly enhances tHO following acute musculoskeletal extremity injury in the presence and absence of blast overpressure. Furthermore, the influence of BOP on tHO cannot be accounted for either in regards to systemic inflammation induced from remote injury or inflammatory-osteo-chondrogenic expression changes local to the musculoskeletal trauma, suggesting that another mechanism beyond BOP and BU synergistic effects are at play. Therefore, these findings warrant future investigations to explore other mechanisms by which blast and burn influence tHO, and testing prophylactic measures to mitigate the local and systemic inflammatory effects of these injuries on development of HO.


Assuntos
Traumatismos por Explosões , Queimaduras , Ossificação Heterotópica , Humanos , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Osteogênese , Qualidade de Vida , Queimaduras/complicações , Traumatismos por Explosões/complicações , Extremidades , Fatores de Risco , Ossificação Heterotópica/prevenção & controle
12.
Scand J Gastroenterol ; 59(5): 608-614, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38333956

RESUMO

BACKGROUND AND AIMS: Accurate polyp size estimation during colonoscopy has an impact on clinical decision-making. A laser-based virtual scale endoscope (VSE) is available to allow measuring polyp size using a virtual adaptive scale. This study evaluates video-based polyp size measurement accuracy among expert endoscopists using either VSE or visual assessment (VA) with either snare as reference size or without any reference size information. METHODS: A prospective, video-based study was conducted with 10 expert endoscopists. Video sequences from 90 polyps with known reference size (fresh specimen measured using calipers) were distributed on three different slide sets so that each slide set showed the same polyp only once with either VSE, VA or snare-based information. A slide set was randomly assigned to each endoscopist. Endoscopists were asked to provide size estimation based on video review. RESULTS: Relative accuracies for VSE, VA, and snare-based estimation were 75.1% (95% CI [71.6-78.5]), 65.0% (95% CI [59.5-70.4]) and 62.0% (95% CI [54.8-69.0]), respectively. VSE yielded significantly higher relative accuracy compared to VA (p = 0.002) and to snare (p = 0.001). A significantly lower percentage of polyps 1-5 mm were misclassified as >5 mm using VSE versus VA and snare (6.52% vs. 19.6% and 17.5%, p = 0.004) and a significantly lower percentage of polyps >5 mm were misclassified as 1-5 mm using VSE versus VA and snare (11.4% vs. 31.9% and 14.9%, p = 0.038). CONCLUSIONS: Endoscopists estimate polyp size with the highest accuracy when virtual adaptive scale information is displayed. Using a snare to assist sizing did not improve measurement accuracy compared to displaying visual information alone.


Assuntos
Pólipos do Colo , Colonoscopia , Gravação em Vídeo , Humanos , Estudos Prospectivos , Colonoscopia/métodos , Pólipos do Colo/patologia , Competência Clínica , Masculino , Feminino
13.
Cancer Epidemiol Biomarkers Prev ; 33(2): 183-185, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38317627

RESUMO

Implementing fecal immunochemical testing (FIT) through clinic based opportunistic screening or programmatic mailing is not as straightforward as it seems. Liu and colleagues present data for 56,980 individuals who submitted a FIT in a safety net hospital system. In 10.2% (N = 5,819), the test was deemed unsatisfactory. These data demonstrate that there is significant room for improvement in clinical practice regarding colorectal cancer screening with FIT. The high rate of 10% for unsatisfactory FIT tests is higher than the 5% benchmark suggested by the U.S. Multi-Society Task Force on colorectal cancer screening. To maximize FIT success, there needs to be a preoccupation with failure at the system level that results in reducing the number of FIT tests that are rejected. Completing a stool test independently at home is not easy. The medical system needs to help and support individuals in completing the test every step of the way. Suggestions include patient related tips such as labelling and mailing the tests. There are also suggestions for the ordering clinician including administrative tracking to notify clinicians when a FIT has not been performed or is rejected. Papers like this get us focused exactly where we need to be to improve FIT-based screening. See related article by Liu et al., p. 215.


Assuntos
Neoplasias Colorretais , Programas de Rastreamento , Humanos , Programas de Rastreamento/métodos , Sangue Oculto , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Detecção Precoce de Câncer/métodos , Fezes
14.
Ophthalmic Surg Lasers Imaging Retina ; 55(2): 112-115, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38198605

RESUMO

This case series reports on two patients who developed macular holes while on prostaglandin analogs (PGA) therapy. The first case involves a 63-year-old woman with a history of a macular hole of the left eye that had spontaneously closed. After starting PGA therapy for elevated intraocular pressure, cystoid macular edema formed, which resulted in reopening of the macular hole. The second case involves a 64-year-old man with primary open-angle glaucoma, on PGA therapy, with a newly diagnosed small macular hole of the right eye that closed after cessation of the PGA therapy. These cases demonstrate an association between prostaglandin analogs and the formation or reopening of full-thickness macular holes. [Ophthalmic Surg Lasers Imaging Retina 2024;55:112-115.].


Assuntos
Glaucoma de Ângulo Aberto , Edema Macular , Perfurações Retinianas , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Perfurações Retinianas/induzido quimicamente , Perfurações Retinianas/diagnóstico , Prostaglandinas , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Edema Macular/induzido quimicamente , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Prostaglandinas Sintéticas/efeitos adversos
15.
Neuropsychol Rev ; 34(1): 155-191, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36725781

RESUMO

Olfactory training (OT), or smell training,consists of repeated exposure to odorants over time with the intended neuroplastic effect of improving or remediating olfactory functioning. Declines in olfaction parallel declines in cognition in various pathological conditions and aging. Research suggests a dynamic neural connection exists between olfaction and cognition. Thus, if OT can improve olfaction, could OT also improve cognition and support brain function? To answer this question, we conducted a systematic review of the literature to determine whether there is evidence that OT translates to improved cognition or altered brain morphology and connectivity that supports cognition. Across three databases (MEDLINE, Scopus, & Embase), 18 articles were identified in this systematic review. Overall, the reviewed studies provided emerging evidence that OT is associated with improved global cognition, and in particular, verbal fluency and verbal learning/memory. OT is also associated with increases in the volume/size of olfactory-related brain regions, including the olfactory bulb and hippocampus, and altered functional connectivity. Interestingly, these positive effects were not limited to patients with smell loss (i.e., hyposmia & anosmia) but normosmic (i.e., normal ability to smell) participants benefitted as well. Implications for practice and research are provided.


Assuntos
Encéfalo , Cognição , Treinamento Olfativo , Humanos , Transtornos do Olfato/terapia , Olfato
17.
Chemistry ; 30(12): e202304070, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38117748

RESUMO

Bicyclo[1.1.1]pentane (BCP) derivatives have attracted significant recent interest in drug discovery as alkyne, tert-butyl and arene bioisosteres, where their incorporation is frequently associated with increased compound solubility and metabolic stability. While strategies for functionalisation of the bridgehead (1,3) positions are extensively developed, platforms allowing divergent substitution at the bridge (2,4,5) positions remain limited. Recent reports have introduced 1-electron strategies for arylation and incorporation of a small range of other substituents, but are limited in terms of scope, yields or practical complexity. Herein, we show the synthesis of diverse 1,2,3-trifunctionalised BCPs through lithium-halogen exchange of a readily accessible BCP bromide. When coupled with medicinally relevant product derivatisations, our developed 2-electron "late stage" approach provides rapid and straightforward access to unprecedented BCP structural diversity (>20 hitherto-unknown motifs reported). Additionally, we describe a method for the synthesis of enantioenriched "chiral-at-BCP" bicyclo[1.1.1]pentanes through a novel stereoselective bridgehead desymmetrisation.

18.
MethodsX ; 11: 102476, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38053622

RESUMO

Canine infectious respiratory disease (CIRD) is a complicated respiratory syndrome in dogs [1], [2], [3]. A panel PCR was developed [4] to detect nine pathogens commonly associated with CIRD: Mycoplasma cynos, Mycoplasma canis, Bordetella bronchiseptica; canine adenovirus type 2, canine herpesvirus 1, canine parainfluenza virus, canine distemper virus, canine influenza virus and canine respiratory coronavirus [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. To evaluate diagnostic performance of the assay, 740 nasal swab and lung tissue samples were collected and tested with the new assay, and compared to an older version of the assay detecting the same pathogens except that it does not differentiate the two Mycoplasma species. Results indicated that the new assay had the same level of specificity, but with higher diagnostic sensitivity and had identified additional samples with potential co-infections. To confirm the new assay is detecting the correct pathogens, samples with discrepant results between the two assays were sequence-confirmed. Spiking a high concertation target to samples carrying lower concentrations of other targets was carried out and the results demonstrated that there was no apparent interference among targets in the same PCR reaction. Another spike-in experiment was used to determine detection sensitivity between nasal swab and lung tissue samples, and similar results were obtained.•A nine-pathogen CIRD PCR panel assay had identified 139 positives from 740 clinical samples with 60 co-infections;•High-concentration target does not have apparent effect on detecting low-concentration targets;•Detection sensitivity were similar between nasal swab and lung tissue samples.

19.
Nature ; 623(7989): 927-931, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37968403

RESUMO

In recent years, certain luminous extragalactic optical transients have been observed to last only a few days1. Their short observed duration implies a different powering mechanism from the most common luminous extragalactic transients (supernovae), whose timescale is weeks2. Some short-duration transients, most notably AT2018cow (ref. 3), show blue optical colours and bright radio and X-ray emission4. Several AT2018cow-like transients have shown hints of a long-lived embedded energy source5, such as X-ray variability6,7, prolonged ultraviolet emission8, a tentative X-ray quasiperiodic oscillation9,10 and large energies coupled to fast (but subrelativistic) radio-emitting ejecta11,12. Here we report observations of minutes-duration optical flares in the aftermath of an AT2018cow-like transient, AT2022tsd (the 'Tasmanian Devil'). The flares occur over a period of months, are highly energetic and are probably nonthermal, implying that they arise from a near-relativistic outflow or jet. Our observations confirm that, in some AT2018cow-like transients, the embedded energy source is a compact object, either a magnetar or an accreting black hole.

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