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1.
J Hematol ; 13(3): 116-120, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38993734

RESUMO

Hemoglobin Korle-Bu (Hb KB) is a rare and likely under-reported hemoglobin (Hb) variant resulting from an unusual point mutation on the beta-globin chain. Hb KB is typically clinically silent, and there are limited reports of Hb KB heterozygosity compounded with other hemoglobinopathies that can present with varying clinical phenotypes. Here, we report a case of compound Hb KB heterozygosity with Hb S in an asymptomatic military trainee with a positive sickle cell screening test. Hb capillary and gel electrophoresis predicted a compound Hb S/D-Punjab overlap, which foretells a severe clinical phenotype. Sequencing of the Hb beta gene HBB demonstrated Hb KB, allowing for a diagnosis that fit his asymptomatic clinical phenotype and allowed for retention in the military.

2.
Eur Radiol ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900281

RESUMO

OBJECTIVES: Artificial intelligence (AI) tools are becoming more available in modern healthcare, particularly in radiology, although less attention has been paid to applications for children and young people. In the development of these, it is critical their views are heard. MATERIALS AND METHODS: A national, online survey was publicised to UK schools, universities and charity partners encouraging any child or young adult to participate. The survey was "live" for one year (June 2022 to 2023). Questions about views of AI in general, and in specific circumstances (e.g. bone fractures) were asked. RESULTS: One hundred and seventy-one eligible responses were received, with a mean age of 19 years (6-23 years) with representation across all 4 UK nations. Most respondents agreed or strongly agreed they wanted to know the accuracy of an AI tool that was being used (122/171, 71.3%), that accuracy was more important than speed (113/171, 66.1%), and that AI should be used with human oversight (110/171, 64.3%). Many respondents (73/171, 42.7%) felt AI would be more accurate at finding problems on bone X-rays than humans, with almost all respondents who had sustained a missed fracture strongly agreeing with that sentiment (12/14, 85.7%). CONCLUSIONS: Children and young people in our survey had positive views regarding AI, and felt it should be integrated into modern healthcare, but expressed a preference for a "medical professional in the loop" and accuracy of findings over speed. Key themes regarding information on AI performance and governance were raised and should be considered prior to future AI implementation for paediatric healthcare. CLINICAL RELEVANCE STATEMENT: Artificial intelligence (AI) integration into clinical practice must consider all stakeholders, especially paediatric patients who have largely been ignored. Children and young people favour AI involvement with human oversight, seek assurances for safety, accuracy, and clear accountability in case of failures. KEY POINTS: Paediatric patient's needs and voices are often overlooked in AI tool design and deployment. Children and young people approved of AI, if paired with human oversight and reliability. Children and young people are stakeholders for developing and deploying AI tools in paediatrics.

3.
Mil Med ; 189(7-8): e1835-e1838, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38720563

RESUMO

Testicular malignancies commonly affect adolescent and young adult males. Although they tend to respond well to cisplatin-based chemotherapy with excellent overall survival, complications such as inferior vena cava tumor thrombus are rare and can be associated with high morbidity and mortality. We present a case of tumor thrombus in a 21-year-old active duty male with a newly diagnosed stage IIIB non-seminomatous germ cell tumor presenting with extensive left lower extremity swelling. Ultrasound with Doppler was notable for significant thrombus of the left common femoral, femoral, and popliteal vein. Computed tomography imaging revealed extensive thrombus of the inferior vena cava, left iliac veins, and left gonadal vein with sparing of the left renal vein. Endovascular thrombectomy was performed with pathologic analysis confirming the presence of malignant cells consistent with tumor thrombus. The patient continued subsequent non-seminomatous germ cell tumor treatment without complications.


Assuntos
Militares , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/complicações , Neoplasias Testiculares/complicações , Adulto Jovem , Trombose/etiologia , Trombose/complicações , Veia Cava Inferior , Tomografia Computadorizada por Raios X/métodos , Trombectomia/métodos
4.
Climacteric ; : 1-9, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695491

RESUMO

OBJECTIVE: This study aimed to examine physicians' and patients' perceptions regarding symptom burden and impact in women experiencing natural vasomotor symptoms (nVMS) or vasomotor symptoms induced by endocrine therapy for breast cancer (iVMS). METHODS: The cross-sectional survey based on real-world clinical consultations was conducted in the USA and five European countries. Obstetrician-gynecologists, primary-care physicians and oncologists provided demographic and symptom data for patients experiencing VMS; patients optionally self-reported their experiences via questionnaires, including their symptom profile and work/activity burden through the Menopause Quality of Life (MENQOL) and Work Productivity and Activity Impairment (WPAI) tools. RESULTS: Physicians completed survey forms on 2451 consulting patients; patients completed 1029 questionnaires. nVMS and iVMS severity was significantly associated with the severity of mood symptoms and sleep disturbances (p < 0.0001). However, around half of the patients with mild nVMS/iVMS also experienced moderate-severe mood changes (55.4%/43.7%) or sleep disturbances (42.4%/40.4%). Presence of mood/sleep disturbances alongside nVMS increased MENQOL vasomotor scores (p = 0.004/p < 0.001). Presence of sleep disturbances increased WPAI activity impairment (p < 0.001) but mood changes did not. Similar findings were reported for iVMS patients. CONCLUSION: Significant burden from the triad of natural or induced menopausal symptoms, sleep disturbances and mood changes affected women's daily activities, work and quality of life more than vasomotor symptoms alone.

5.
Kidney Int ; 106(1): 24-34, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38614389

RESUMO

Kidney epithelial cells have very high energy requirements, which are largely met by fatty acid oxidation. Complex changes in lipid metabolism are observed in patients with kidney disease. Defects in fatty acid oxidation and increased lipid uptake, especially in the context of hyperlipidemia and proteinuria, contribute to this excess lipid build-up and exacerbate kidney disease development. Recent studies have also highlighted the role of increased de novo lipogenesis in kidney fibrosis. The defect in fatty acid oxidation causes energy starvation. Increased lipid uptake, synthesis, and lower fatty acid oxidation can cause toxic lipid build-up, reactive oxygen species generation, and mitochondrial damage. A better understanding of these metabolic processes may open new treatment avenues for kidney diseases by targeting lipid metabolism.


Assuntos
Ácidos Graxos , Túbulos Renais , Metabolismo dos Lipídeos , Humanos , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Animais , Ácidos Graxos/metabolismo , Nefropatias/metabolismo , Nefropatias/patologia , Mitocôndrias/metabolismo , Lipogênese , Oxirredução , Fibrose , Espécies Reativas de Oxigênio/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Metabolismo Energético
6.
Cureus ; 16(3): e56237, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38618451

RESUMO

We present a rare case of hemophagocytic lymphohistiocytosis (HLH) secondary to nasal-type extranodal natural killer/T-cell lymphoma (ENKL). Nasal-type ENKL is a rare subtype of non-Hodgkin's lymphoma usually associated with Epstein-Barr virus (EBV). The patient was a 19-year-old woman who presented with facial numbness, diminished hearing, and dysgeusia. She was febrile with palatal necrosis, loss of gag reflex, and cranial nerve palsies. Labs revealed neutropenia. Broad-spectrum antimicrobials, including amphotericin, were started. Given concern for invasive fungal disease, she underwent surgical debridement, which revealed inflamed fibrous tissue and extensive necrosis. Pathology showed no fungal elements or malignancy. Lack of clinical improvement and worsening palatal necrosis prompted additional debridement. Histology identified an atypical CD3+/CD56+ cellular infiltrate. Bone marrow biopsy showed prominent hemophagocytosis, but no malignancy. She met the criteria for HLH and high-dose dexamethasone was started. Her fevers resolved. Additional labs and nasal tissue sampling with EBV-encoded RNA staining were recommended. Flow cytometry was negative, but histology revealed ENKL nasal-type, with positive EBV-encoded RNA in situ hybridization. Plasma EBV DNA level was 11,518 IU/mL. The M-SMILE (dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide) regimen was initiated; one cycle led to marked improvement. EBV level returned to zero. Subsequent radiation and chemotherapy, followed by autologous stem cell transplant consolidation, led to complete remission. We conclude that ENKL may mimic invasive sinusitis clinically. Fibrinoid necrosis in vessels and surrounding tissues often leads to diagnostic delay. It is important to have a high degree of clinical suspicion for malignancy in cases of HLH and sinusitis unresponsive to appropriate therapy. Obtaining proper tissue, communication with the pathologist, and prompt initiation of therapy are crucial.

7.
Psychooncology ; 33(3): e6313, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38446532

RESUMO

OBJECTIVE: Support people of cancer patients are at significant risk for psychological distress. Additionally, cancer patients' well-being is reciprocally associated with support peoples' psychological well-being. Informed by Uncertainty in Illness Theory, this study tests whether support person psychological well-being is influenced by provider communication and uncertainty reduction. METHODS: We tested a multiple mediation model to investigate how empathic communication facilitates psychological adjustment in support people of cancer patients and how this process is mediated by support peoples' illness uncertainty and caregiver burden. Support people of cancer patients (N = 121; including spouses, adult children, etc.) completed an online questionnaire about their perceptions of oncologists' empathy, uncertainty about the cancer patients' illness, perceived caregiving burden, and their psychological adjustment to diagnoses. RESULTS: Path analysis revealed that (1) more perceived oncologist empathy was associated with less illness uncertainty, (2) more illness uncertainty was associated with worse psychological adjustment and more perceived caregiver burden, and (3) more burden was associated with worse adjustment (χ2 (2) = 1.19, p = 0.55; RMSEA < 0.01; CFI = 1.00; SRMR = 0.02). CONCLUSIONS: Given the reciprocal nature of well-being between cancer patients and their support people, it is critical to understand and bolster support people's psychological well-being. Results demonstrated how empathic provider communication can support psychological well-being for support people of cancer patients. Additionally, this study offers theoretical contributions to understandings of illness uncertainty in caregiver populations.


Assuntos
Neoplasias , Oncologistas , Adulto , Humanos , Ajustamento Emocional , Incerteza , Filhos Adultos
8.
Allergy Asthma Clin Immunol ; 20(1): 17, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409099

RESUMO

In this letter to the editor, we present questionnaire-based data assessing the patient journey of adults with moderate-severe Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) in the USA and five European countries. These data highlight how long and difficult the patient journey with CRSwNP can be and how improved disease awareness among physicians could lead to more timely diagnosis and treatment, and hence improved management of patients.

9.
Plast Reconstr Surg ; 153(2): 334e-347e, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37163479

RESUMO

BACKGROUND: Current minimally invasive fat reduction modalities use equipment that can cost thousands of U.S. dollars. Electrochemical lipolysis (ECLL), using low-cost battery and electrodes (approximately $10), creates acid/base within fat (width, approximately 3 mm), damaging adipocytes. Longitudinal effects of ECLL have not been studied. In this pilot study, the authors hypothesize that in vivo ECLL induces fat necrosis, decreases adipocyte number/viability, and forms lipid droplets. METHODS: Two female Yorkshire pigs (50 to 60 kg) received ECLL. In pig 1, 10 sites received ECLL, and 10 sites were untreated. In pig 2, 12 sites received ECLL and 12 sites were untreated. For ECLL, two electrodes were inserted into dorsal subcutaneous fat and direct current was applied for 5 minutes. Adverse effects of excessive pain, bleeding, infection, and agitation were monitored. Histology, live-dead (calcein, Hoechst, ethidium homodimer-1), and morphology (Bodipy and Hoechst) assays were performed on day 0 and postprocedure days 1, 2, 7, 14 (pig 1 and pig 2), and 28 (pig 2). Average particle area, fluorescence signal areas, and adipocytes and lipid droplet numbers were compared. RESULTS: No adverse effects occurred. Live-dead assays showed adipocyte death on the anode on days 0 to 7 and the cathode on days 1 to 2 (not significant). Bodipy showed significant adipocyte loss at all sites ( P < 0.001) and lipid droplet formation at the cathode site on day 2 ( P = 0.0046). Histology revealed fat necrosis with significant increases in average particle area at the anode and cathode sites by day 14 (+277.3% change compared with untreated, P < 0.0001; +143.4%, P < 0.0001) and day 28 (+498.6%, P < 0.0001; +354.5%, P < 0.0001). CONCLUSIONS: In vivo ECLL induces fat necrosis in pigs. Further studies are needed to evaluate volumetric fat reduction. CLINICAL RELEVANCE STATEMENT: In vivo ECLL induces adipocyte death and fat necrosis. ECLL has the potential to be utilized in body fat contouring.


Assuntos
Compostos de Boro , Necrose Gordurosa , Lipólise , Feminino , Animais , Suínos , Projetos Piloto , Adipócitos
10.
JMIR Mhealth Uhealth ; 11: e47371, 2023 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-37831493

RESUMO

BACKGROUND: Stress-related mental health disorders have steadily increased and contributed to a worldwide disease burden with up to 50% experiencing a stress-related mental health disorder worldwide. Data suggest that only approximately 20%-65% of individuals receive treatment. This gap in receiving treatment may be attributed to barriers such as limited treatment access, negative stigma surrounding mental health treatment, approachability (ie, not having a usual treatment plan or provider), affordability (ie, lack of insurance coverage and high treatment cost), and availability (ie, long waits for appointments) leaving those who need treatment without necessary care. To mitigate the limited access mental health treatment, there has been a rise in the application and study of digital mental health interventions. As such, there is an urgent need and opportunity for effective digital mental health interventions to alleviate stress symptoms, potentially reducing adverse outcomes of stress-related disorders. OBJECTIVE: This study examined if app-based guided mindfulness could improve subjective levels of stress and influence physiological markers of stress reactivity in a population with elevated symptoms of stress. METHODS: The study included 163 participants who had moderate to high perceived stress as assessed by the Perceived Stress Scale (PSS-10). Participants were randomly allocated to 1 of 5 groups: a digital guided program designed to alleviate stress (Managing Stress), a digital mindfulness fundamentals course (Basics), digitally delivered breathing exercises, an active control intervention (Audiobook), and a Waitlist Control group. The 3 formats of mindfulness interventions (Managing Stress, Basics, and Breathing) all had a total duration of 300 minutes spanning 20-30 days. Primary outcome measures were perceived stress using the PSS-10, self-reported sleep quality using the Pittsburgh Sleep Quality Index, and trait mindfulness using the Mindful Attention Awareness Scale. To probe the effects of physiological stress, an acute stress manipulation task was included, specifically the cold pressor task (CPT). Heart rate variability was collected before, during, and after exposure to the CPT and used as a measure of physiological stress. RESULTS: The results showed that PSS-10 and Pittsburgh Sleep Quality Index scores for the Managing Stress (all P<.001) and Basics (all P≤.002) groups were significantly reduced between preintervention and postintervention periods, while no significant differences were reported for the other groups. No significant differences among groups were reported for Mindful Attention Awareness Scale (P=.13). The physiological results revealed that the Managing Stress (P<.001) and Basics (P=.01) groups displayed reduced physiological stress reactivity between the preintervention and postintervention periods on the CPT. There were no significant differences reported for the other groups. CONCLUSIONS: These results demonstrate efficacy of app-based mindfulness in a population with moderate to high stress on improving self-reported stress, sleep quality, and physiological measures of stress during an acute stress manipulation task. TRIAL REGISTRATION: ClinicalTrials.gov NCT05832632; https://www.clinicaltrials.gov/ct2/show/NCT05832632.


Assuntos
Atenção Plena , Aplicativos Móveis , Humanos , Atenção Plena/métodos , Saúde Mental , Estresse Fisiológico , Agendamento de Consultas
11.
Health Commun ; : 1-18, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37559483

RESUMO

Provider empathy is a crucial component in establishing therapeutic provider-patient relationships. The benefits of increased perceptions of empathy can support patient psychological adjustment to their cancer as well as patients' comfort and confidence in disclosing to providers, ultimately promoting patient engagement. Guided by the disclosure decision-making model, this manuscript explores how perceptions of empathy influence patient psychological adjustment and how those variables influence patient disclosure efficacy. The model ultimately predicts patient sharing and withholding of information during the medical interaction. This study tested a mediation model to investigate how current (n = 111) and former (n = 174) breast cancer patients' psychological adjustment mediates the relationship between patient perceptions of oncologist empathic communication and efficacy to disclose health information to their oncologist and their disclosure enactment in sharing and withholding. Overall, former patients compared to current patients had more positive perceptions of their oncologist's empathic communication, had better psychological adjustment, felt more self-efficacy to disclose to their oncologist, and shared more and withheld less information from their oncologist (p < .05 in all cases). Structural equation modeling revealed good fit to the data for both current and former patients such that more perceived empathic communication was associated with more efficacy for disclosure, which was associated with more sharing and less withholding. Additionally, there was an indirect relationship from perceptions of empathic communication to disclosure efficacy through patients' psychological adjustment to the diagnosis. Results reinforce the importance of providers' empathic communication for cancer patients' psychological adjustment because patient sharing and withholding of information remain crucially important to achieving holistic care across the cancer trajectory.

12.
Patient Educ Couns ; 114: 107791, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37244129

RESUMO

OBJECTIVES: This study examined the degree to which breast cancer patients' psychological well-being is facilitated through empathic provider communication. We explored symptom/prognostic uncertainty reduction as a mechanism through which provider communication influences patient psychological adjustment. Additionally, we tested if treatment status moderates this relationship. METHODS: Informed by uncertainty in illness theory, current (n = 121) and former (n = 187) breast cancer patients completed questionnaires about perceptions of their oncologists' empathy and their symptom burden, uncertainty, and adjustment to their diagnosis. Structural equation modeling (SEM) was conducted to test hypothesized relationships between perceived provider empathic communication, uncertainty, symptom burden, and psychological adjustment. RESULTS: SEM supported the following: (1) higher symptom burden was associated with increased uncertainty and reduced psychological adjustment, (2) lower uncertainty was associated with increased adjustment, and (3) increased empathic communication was associated with lower symptom burden and uncertainty for all patients (χ2(139) = 307.33, p < .001; RMSEA = .063 (CI .053, .072); CFI = .966; SRMR = .057). Treatment status moderated these relationships (Δχ2 = 264.07, Δdf = 138, p < .001) such that the strength of the relationship between uncertainty and psychological adjustment was stronger for former patients than for current patients. CONCLUSIONS: Results of this study reinforce the importance of perceptions of provider empathic communication as well as the potential benefits of eliciting and addressing patient uncertainty about treatment and prognosis throughout the cancer care continuum. PRACTICE IMPLICATIONS: Patient uncertainty should be a priority for cancer-care providers both throughout and post-treatment for breast cancer patients.


Assuntos
Neoplasias da Mama , Empatia , Humanos , Feminino , Neoplasias da Mama/terapia , Incerteza , Ajustamento Emocional , Comunicação
13.
Microbiol Resour Announc ; 12(5): e0002323, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37036373

RESUMO

Chop, DelRio, and GrandSlam are phage with a Siphoviridae morphotype isolated from soil in Arkansas using the host Gordonia terrae 3612. All three are temperate, and their genomes share at least 96% nucleotide identity. These phage are assigned to cluster DI based on gene content similarity to other sequenced actinobacteriophage.

16.
Respir Care ; 68(1): 8-17, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36566031

RESUMO

BACKGROUND: In the midst of the COVID-19 pandemic, noninvasive respiratory support (NRS) therapies such as high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) were central to respiratory care. The extent to which these treatments increase the generation and dispersion of infectious respiratory aerosols is not fully understood. The objective of this study was to characterize SARS-CoV-2 aerosol dispersion from subjects with COVID-19 undergoing NRS therapy. METHODS: Several different aerosol sampling devices were used to collect air samples in the vicinity of 31 subjects with COVID-19, most of whom were receiving NRS therapy, primarily HFNC. Aerosols were collected onto filters and analyzed for the presence of SARS-CoV-2 RNA. Additional measurements were collected in an aerosol chamber with healthy adult subjects using respiratory therapy devices under controlled and reproducible conditions. RESULTS: Fifty aerosol samples were collected from subjects receiving HFNC or NIV therapy, whereas 6 samples were collected from subjects not receiving NRS. Only 4 of the 56 aerosol samples were positive for SARS-CoV-2 RNA, and all positive samples were collected using a high air flow scavenger mask collection device placed in close proximity to the subject. The chamber measurements with healthy subjects did not show any significant increase in aerosol dispersion caused by the respiratory therapy devices compared to baseline. CONCLUSIONS: Our findings demonstrate very limited detection of SARS-CoV-2-containing aerosols in the vicinity of subjects with COVID-19 receiving NRS therapies in the clinical setting. These results, combined with controlled chamber measurements showing that HFNC and NIV device usage was not associated with increased aerosol dispersion, suggest that NRS therapies do not result in increased dispersal of aerosols in the clinical setting.


Assuntos
COVID-19 , Ventilação não Invasiva , Adulto , Humanos , COVID-19/terapia , SARS-CoV-2 , Pandemias , RNA Viral , Aerossóis e Gotículas Respiratórios , Ventilação não Invasiva/métodos , Cânula , Oxigenoterapia/métodos
17.
JPEN J Parenter Enteral Nutr ; 47(3): 354-363, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36398422

RESUMO

BACKGROUND: 100% soybean oil emulsions (SO100) are associated with poor docosahexaenoic acid (DHA) and arachidonic acid (ARA) status in extremely low birth weight (ELBW) infants. A multi-oil emulsion with 15% fish oil (FO15) contains more DHA and ARA than SO100. This study compares clinical outcomes, namely growth and fatty acids, in ELBW infants who received S0100 or FO15. METHODS: This observational study included ELBW infants born between 2014 and 2019 who received SO100 or FO15 for >7 days. Gas chromatography/mass spectrometry was used to measure erythrocyte fatty acids. RESULTS: The mean ± SD gestational age was 27 ± 3 and 26 ± 2 weeks for SO100 (n = 43) and FO15 (n = 43), respectively (P = 0.2). DHA (-0.3 ± 0.10% per week, P = 0.026, for FO15 vs -0.2 ± 0.05% per week, P < 0.001, for SO100) and ARA (-0.8 ± 0.21% per week for FO15 vs -0.9 ± 0.17% per week for SO100; P < 0.001 for both) declined in both groups with no difference between groups (P interaction > 0.7 for both). After controlling for days to reach full feeds, the mean difference in weight z score trajectories was similar (Est = -0.08; 95% CI, -0.82 to 0.04; P = 0.2), and SO100 was associated with a nonsignificant increased odds for cholestasis (odds ratio, 3.1; 95% CI, 0.96-10.2; P = 0.059). There was no difference in other clinical comorbidities. CONCLUSIONS: In comparison with ELBW infants who received SO100, infants who received FO15 still demonstrated a decline in DHA and ARA. Growth and other clinical outcomes were unchanged.


Assuntos
Óleos de Peixe , Nutrição Parenteral , Recém-Nascido , Humanos , Emulsões/química , Nutrição Parenteral/métodos , Recém-Nascido Prematuro , Óleo de Soja , Ácidos Docosa-Hexaenoicos , Ácido Araquidônico
18.
Cell ; 185(20): 3720-3738.e13, 2022 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-36103894

RESUMO

Necrosis of macrophages in the granuloma, the hallmark immunological structure of tuberculosis, is a major pathogenic event that increases host susceptibility. Through a zebrafish forward genetic screen, we identified the mTOR kinase, a master regulator of metabolism, as an early host resistance factor in tuberculosis. We found that mTOR complex 1 protects macrophages from mycobacterium-induced death by enabling infection-induced increases in mitochondrial energy metabolism fueled by glycolysis. These metabolic adaptations are required to prevent mitochondrial damage and death caused by the secreted mycobacterial virulence determinant ESAT-6. Thus, the host can effectively counter this early critical mycobacterial virulence mechanism simply by regulating energy metabolism, thereby allowing pathogen-specific immune mechanisms time to develop. Our findings may explain why Mycobacterium tuberculosis, albeit humanity's most lethal pathogen, is successful in only a minority of infected individuals.


Assuntos
Mycobacterium marinum , Mycobacterium tuberculosis , Tuberculose , Animais , Mycobacterium tuberculosis/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Peixe-Zebra
19.
Maturitas ; 164: 38-45, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35785563

RESUMO

OBJECTIVES: This study elicited the views of physicians and patients with vasomotor symptoms (VMS) associated with menopause on the impact of VMS and treatment patterns/perceptions. STUDY DESIGN: Data from the Adelphi VMS Disease Specific Programme, a point-in-time survey conducted in 5 European countries and the United States in 2020, were used. Primary care providers (PCPs) and gynecologists seeing ≥3 patients/week with VMS associated with menopause completed a survey and chart review; their patients were invited to complete a survey and questionnaires. MAIN OUTCOME MEASURES: Physicians reported treatment patterns and patient-specific symptoms and treatment preferences. Patients described symptoms, impact of VMS, and treatment satisfaction. RESULTS: Participants included 115 PCPs and 118 gynecologists. Physicians reviewed the charts of 1816 patients, 854 of whom completed surveys. Moderate/severe impact of VMS on sleep, mood, quality of life, and work/study was reported by 35.8 %, 31.6 %, 23.6 %, and 15.4 % of women, respectively. Based on chart review, 64.8 % of women were currently prescribed treatment for VMS, most commonly hormone therapy (HT; 73.1 %), followed by selective serotonin or serotonin-norepinephrine reuptake inhibitors (31.3 %). Most women (57.3 %) with VMS were eligible for HT but averse to using it. Despite 91.4 % of physicians finding HT to be effective, 62.7 % agreed (slightly-strongly) that their patients are generally reluctant to use it. One-third of women were dissatisfied with VMS control. CONCLUSIONS: VMS can considerably impact daily life. Effective treatment options that are better accepted could potentially improve management of VMS and lead to better quality of life for women with VMS associated with menopause. CLINICAL TRIAL REGISTRATION: None.


Assuntos
Fogachos , Médicos , Feminino , Fogachos/tratamento farmacológico , Humanos , Menopausa , Qualidade de Vida , Serotonina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Estados Unidos
20.
Int J Transl Sci ; 2(1)2022.
Artigo em Inglês | MEDLINE | ID: mdl-35799866

RESUMO

To investigate how the structure of Sharpey's fibers in the periodontal ligaments (PDL) were affected by experimental periodontitis in a young pig model, 7 were periodically inoculated with four types of bacteria and a ligature around the last maxillary molar for 8 weeks to induce periodontitis (PG), and 10 served as controls (CG). The harvested molar blocks were sectioned coronally and stained with either hematoxylin & eosin (H&E) or Sirius Red (SR). The H&E-stained images were first reviewed. Then, images of each adjacent SR-stained sections were captured at the region close to the apex of mesial roots under polarizing light microscopy. Sharpey's fiber numbers in each bundle, total bundle numbers, connection of the bundle to the cementum and alveoli, as well as bundle angulations to the molar long axis were quantified in the defined area 500µm apical to the root apex. Compared to CG, PG showed the following features: 15.13% less total bundle number; 17.8% less bundle size; significantly less connected fiber bundles; 9.2% more interrupted fiber bundles; and 3.85% more oriented toward the cervical in the bundle angulation. These results suggest that experimental periodontitis alters the PDL structure, leading to more interruptions of Sharpey's fiber attachments to the cementum.

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