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1.
Med J Malaysia ; 79(5): 531-537, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39352154

RESUMEN

INTRODUCTION: With the current trend of increasing noncommunicable diseases (NCD), like hypertension, diabetes and dyslipidaemia worldwide and in Malaysia, a comprehensive study is essential to find the local population's knowledge, attitude and practice towards NCD. Little is known about the indigenous people of Orang Asli's health conditions and health-seeking behaviours towards these chronic diseases. The study aimed to assess knowledge, attitudes and practices (KAP) status towards non-communicable disease and its association with demographic background among Orang Asli adults of the Semelai subgroup in central Pahang, Malaysia. MATERIALS AND METHODS: A cross-sectional study was conducted among 251 adult Semelai people in Bera district, Pahang. Data was collected through face-to-face interviews to obtain socio-demographic data, KAP towards NCD. Bivariate analysis was performed to test the association between the socio-demographic factor and the KAP score. RESULTS: Among respondents, 57.4% were female, 82.5% were married, and 46.2% completed primary school. The majority were animism believers (83.3%), self-employed (75.3%) and earning less than RM1000 (87.6%). The respondents' ages ranged from 18 to 77, with a mean age of 41.1 (S.D ± 13.9). The prevalence of known type-2 diabetes mellitus (T2DM), hypertension, and dyslipidaemia was 9.6%, 20.7%, and 8.8%, respectively. About 23.1% of respondents have a family history of chronic disease. Regarding KAP parameters, only 12.7% have good knowledge, and 35.5% have good practice in prevention and treatment. However, more than half (59.8%) have a positive attitude towards chronic diseases. This study also showed that higher household income and education levels were positively associated with higher scores of KAP (p < 0.001). CONCLUSION: This study presented a low-to-moderate percentage of Orang Asli who have good KAP towards NCD. KAP levels were significantly associated with education levels and household income. Hence, improving education and poverty in the Orang Asli community may successively increase the knowledge level, impart a positive attitude towards NCDs, and improve the practice level toward treatment and prevention.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Enfermedades no Transmisibles , Humanos , Malasia , Femenino , Masculino , Adulto , Estudios Transversales , Persona de Mediana Edad , Adulto Joven , Pueblos Indígenas/psicología , Adolescente , Anciano
3.
Proc Natl Acad Sci U S A ; 121(36): e2404042121, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39207735

RESUMEN

The course of normal development and response to pathology are strongly influenced by biological sex. For instance, female childhood cancer survivors who have undergone cranial radiation therapy (CRT) tend to display more pronounced cognitive deficits than their male counterparts. Sex effects can be the result of sex chromosome complement (XX vs. XY) and/or gonadal hormone influence. The contributions of each can be separated using the four-core genotype mouse model (FCG), where sex chromosome complement and gonadal sex are decoupled. While studies of FCG mice have evaluated brain differences in adulthood, it is still unclear how sex chromosome and sex hormone effects emerge through development in both healthy and pathological contexts. Our study utilizes longitudinal MRI with the FCG model to investigate sex effects in healthy development and after CRT in wildtype and immune-modified Ccl2-knockout mice. Our findings in normally developing mice reveal a relatively prominent chromosome effect prepubertally, compared to sex hormone effects which largely emerge later. Spatially, sex chromosome and hormone influences were independent of one another. After CRT in Ccl2-knockout mice, both male chromosomes and male hormones similarly improved brain outcomes but did so more separately than in combination. Our findings highlight the crucial role of sex chromosomes in early development and identify roles for sex chromosomes and hormones after CRT-induced inflammation, highlighting the influences of biological sex in both normal brain development and pathology.


Asunto(s)
Encéfalo , Irradiación Craneana , Ratones Noqueados , Cromosomas Sexuales , Animales , Masculino , Femenino , Cromosomas Sexuales/genética , Encéfalo/metabolismo , Encéfalo/efectos de la radiación , Encéfalo/crecimiento & desarrollo , Ratones , Irradiación Craneana/efectos adversos , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Hormonas Esteroides Gonadales/metabolismo , Imagen por Resonancia Magnética
4.
Rev Sci Instrum ; 95(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39115399

RESUMEN

We present a reduced-order model to calculate response matrices rapidly for filter stack spectrometers (FSSs). The reduced-order model allows response matrices to be built modularly from a set of pre-computed photon and electron transport and scattering calculations through various filter and detector materials. While these modular response matrices are not appropriate for high-fidelity analysis of experimental data, they encode sufficient physics to be used as a forward model in design optimization studies of FSSs, particularly for machine learning approaches that require sampling and testing a large number of FSS designs.

5.
Chaos ; 34(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39177957

RESUMEN

Dynamics and properties of breathers for the modified Korteweg-de Vries equations with negative cubic nonlinearities are studied. While breathers and rogue waves are absent in a single component waveguide for the negative nonlinearity case, coupling can induce regimes of modulation instabilities. Such instabilities are correlated with the existence of rogue waves and breathers. Similar scenarios have been demonstrated previously for coupled systems of nonlinear Schrödinger and Hirota equations. Both real- and complex-valued modified Korteweg-de Vries equations will be treated, which are applicable to stratified fluids and optical waveguides, respectively. One special family of breathers for coupled, complex-valued equations is derived analytically. Robustness and stability of breathers are studied computationally. Knowledge of the growth rates of modulation instability of plane waves provides an instructive prelude on the robustness of breathers to deterministic perturbations. A theoretical formulation of the linear instability of breathers will involve differential equations with periodic coefficient, i.e., a Floquet analysis. Breathers associated with larger eigenvalues of the monodromy matrix tend to suffer greater instability and increased tendency of distortion. Predictions based on modulation instability and Floquet analysis show excellent agreements. The same trend is obtained for simulations conducted with random noise disturbances. Linear approaches like modulation instabilities and Floquet analysis, thus, generate a very illuminating picture of the nonlinear dynamics.

6.
Rev Sci Instrum ; 95(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39087818

RESUMEN

We demonstrate the application of neural networks to perform x-ray spectra unfolding from data collected by filter stack spectrometers. A filter stack spectrometer consists of a series of filter-detector pairs, where the detectors behind each filter measure the energy deposition through each layer as photo-stimulated luminescence (PSL). The network is trained on synthetic data, assuming x-rays of energies <1 MeV and of two different distribution functions (Maxwellian and Gaussian) and the corresponding measured PSL values obtained from five different filter stack spectrometer designs. Predicted unfolds of single distributions are near identical reproductions of the ground truth spectra, with differences in the values lower than 20% at the higher energy end in some cases. The neural network has also demonstrated robustness to experimental measurement errors of <5% and some capability of performing unfolds for linear combinations of the two distributions without previous training. The network can perform unfolds at rates >1 Hz, ideal for application to some high-repetition-rate systems.

8.
East Asian Arch Psychiatry ; 34(2): 23-28, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38955787

RESUMEN

BACKGROUND: There is evidence suggesting that autistic traits are associated with schizotypal traits. This study examined the factor structure of the Autism Spectrum Quotient 10 (AQ-10) and its associations with schizotypal traits (measured by the Schizotypal Personality Questionnaire-Brief [SPQ-B]) in a cohort of Chinese adolescents and young adults. METHODS: Invitation letters, stratified by locations and housing types, were randomly sent to individuals aged 15 to 24 years for participation. Assessments were made using face-to-face or online interviews. Autistic traits were assessed using the Chinese version of the AQ-10. Schizotypal personality traits were assessed using the Chinese version of the 22-item SPQ-B. RESULTS: In total, 395 male and 536 female participants (mean age, 19.93 years) were recruited between July 2020 and May 2021. Exploratory factor analysis of the AQ-10 yielded three factors (theory of mind, task switching, and attention deficits) explaining 55.11% of the total variance. Autistic traits were positively correlated with schizotypal traits of disorganised features (r = 0.21, p < 0.001), interpersonal relationship deficits (r = 0.19, p < 0.001), and cognitive-perceptual deficits (r = 0.11, p = 0.001). CONCLUSION: In Chinese adolescents and young adults, autistic traits, especially task switching and attention deficits (compared with theory of mind) are more closely correlated with schizotypal personality traits. Disentangling the overlapping and diametrical structure of autistic traits and schizotypal traits may help understand their aetiologies, assessment, and interventions.


Asunto(s)
Trastorno del Espectro Autista , Trastorno de la Personalidad Esquizotípica , Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Trastorno de la Personalidad Esquizotípica/psicología , Trastorno del Espectro Autista/psicología , Hong Kong , Análisis Factorial , Encuestas y Cuestionarios , Adulto , Teoría de la Mente , Escalas de Valoración Psiquiátrica
10.
Opt Express ; 32(11): 18761-18770, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38859026

RESUMEN

The recent advent of quantum computing has the potential to overhaul security, communications, and scientific modeling. Superconducting qubits are a leading platform that is advancing noise-tolerant intermediate-scale quantum processors. The implementation requires scaling to large numbers of superconducting qubits, circuit depths, and gate speeds, wherein high-purity RF signal generation and effective cabling transport are desirable. Fiber photonic-enhanced RF signal generation has demonstrated the principle of addressing both signal generation and transport requirements, supporting intermediate qubit numbers and robust packaging efforts; however, fiber-based approaches to RF signal distribution are often bounded by their phase instability. Here, we present a silicon photonic integrated circuit-based version of a photonic-enhanced RF signal generator that demonstrates the requisite stability, as well as a path towards the necessary signal fidelity.

11.
Biomed Pharmacother ; 176: 116895, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38876055

RESUMEN

BACKGROUND: Soft tissue sarcomas (STS) are rare diseases typically arising from connective tissues in children and adults. However, chemotherapies involved in the treatment of STS may cause toxic side effects and multi-drug chemoresistance, making the treatment even more challenging. Histone deacetylase inhibitors (HDACi) are epigenetic agents which have shown anti-tumor effects as single agent as well as combination use with other drugs. Our project intends to prove the same effects in STS. METHODS: Panobinostat (LBH589) plus doxorubicin was selected for investigations based on our previous research. Tumor xenografts were tried in an epithelioid sarcoma model to validate good synergy effects in vivo and a leiomyosarcoma model was used as a negative comparison group. Gene profile changes were studied afterwards. The possible pathway changes caused by HDACi were explored and validated by several assays. RESULTS: Synergy effect of LBH589 plus doxorubicin was successfully validated in STS cell lines and an epithelioid sarcoma mice model. We tried to reduce the dose of doxorubicin to a lower level and found the drug combination can still inhibit tumor size in mice. Furthermore, gene profile changes caused by LBH589 was studied by RNA-Sequencing analysis. Results showed LBH589 can exert effects on a group of target genes which can regulate potential biological functions especially in the cell cycle pathway.


Asunto(s)
Doxorrubicina , Sinergismo Farmacológico , Inhibidores de Histona Desacetilasas , Panobinostat , Sarcoma , Ensayos Antitumor por Modelo de Xenoinjerto , Panobinostat/farmacología , Doxorrubicina/farmacología , Animales , Sarcoma/tratamiento farmacológico , Sarcoma/patología , Humanos , Línea Celular Tumoral , Inhibidores de Histona Desacetilasas/farmacología , Ratones , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Ratones Desnudos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos
12.
Hernia ; 28(4): 1365-1372, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38775981

RESUMEN

PURPOSE: To compare the outcome of indirect inguinal hernias repaired by using single-port laparoscopic percutaneous internal ring suture (SPIRS) between the pediatric and adult females. METHODS: The medical records of females who were clinically assessed to have inguinal hernia from Oct. 2016 to May 2022 were reviewed. Patients who received laparoscopy for the diagnosis of the hernia type and customized treatment according to their hernia type were included, while those who chose other operation methods initially were excluded. The patients were divided into the adult and pediatric groups based on their age. The demographic characteristics, hernia types, operation durations, and outcomes were analyzed between these two groups. RESULTS: A total of 65 adults and 60 children were included in this study. The median age was 38 years. (range: 23-88) for group A and 3 years (range: 0.1-16) for group P. Indirect hernias were present in 85% of adults and 100% of children. All the indirect hernias were repaired by SPIRS uneventfully. Incidence of contralateral patent processus vaginalis was 24% in adults and 50% in children (p = 0.016). The average operation time was 22/46 min (one/two sides) for the adults and 9/15 min (one/two sides) for the pediatrics (p < 0.010 for both). The overall complication rates were 5.4% and 3.3% for the adult and pediatric group respectively (p = 0.106). No recurrence was observed in the pediatric group, but two adults experienced recurrence and another had chronic postoperative inguinal pain, necessitating reoperation. The mean follow-up period was 38.6 ± 15.4 months for adults and 42.8 ± 18.9 months for children (p = 0.198). CONCLUSION: Our results support that the pathogenesis of indirect inguinal hernia for the female adults is due to the non-obliteration of a congenital processus vaginalis. Tailored treatment of the female IIH by using single-port laparoscopic percutaneous internal ring suture may be an alternative for the management of female IHs.


Asunto(s)
Hernia Inguinal , Herniorrafia , Laparoscopía , Técnicas de Sutura , Humanos , Hernia Inguinal/cirugía , Femenino , Laparoscopía/métodos , Laparoscopía/efectos adversos , Adulto , Herniorrafia/métodos , Herniorrafia/efectos adversos , Niño , Persona de Mediana Edad , Adulto Joven , Anciano , Preescolar , Adolescente , Estudios Retrospectivos , Anciano de 80 o más Años , Tempo Operativo , Lactante , Factores de Edad , Recurrencia , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología
13.
Hong Kong Med J ; 30(3): 202-208, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38807255

RESUMEN

INTRODUCTION: The Framingham risk model estimates a person's 10-year cardiovascular disease (CVD) risk. This study used this model to calculate the changes in sex- and age-specific CVD risks in the Hong Kong Population Health Survey (PHS) 2014/15 compared with two previous surveys conducted during 2003 and 2005, namely, PHS 2003/2004 and Heart Health Survey (HHS) 2004/2005. METHODS: This study included individuals aged 30 to 74 years from PHS 2014/15 (n=1662; n=4 445 868 after population weighting) and PHS 2003/2004 and HHS 2004/2005 (n=818; n=3 495 074 after population weighting) with complete data for calculating the risk of CVD predicted by the Framingham model. Sex-specific CVD risks were calculated based on age, total cholesterol and high-density lipoprotein cholesterol levels, mean systolic blood pressure, smoking habit, diabetic status, and hypertension treatment. Mean sex- and age-specific CVD risks were calculated; differences in CVD risk between the two surveys were compared by independent t tests. RESULTS: The difference in 10-year CVD risk from 2003-2005 to 2014-2015 was not statistically significant (10.2% vs 10.6%; P=0.29). After age standardisation according to World Health Organization world standard population data, a small decrease in CVD risk was observed, from 9.4% in 2003-2005 to 8.8% in 2014-2015. Analysis according to age-group showed that more participants aged 65 to 74 years were considered high risk in 2003 to 2005 (2003-2005: 66.8% vs 2014-2015: 53.1%; P=0.028). This difference may be due to the decrease in smokers among men (2003-2005: 30.5% vs 2014-2015: 24.0%; P<0.001). CONCLUSION: From 2003-2005 to 2014-2015, there was a small decrease in age-standardised 10-year CVD risk. A holistic public health approach simultaneously targeting multiple risk factors is needed to achieve greater decreases in CVD risk.


Asunto(s)
Enfermedades Cardiovasculares , Encuestas Epidemiológicas , Humanos , Hong Kong/epidemiología , Masculino , Persona de Mediana Edad , Femenino , Enfermedades Cardiovasculares/epidemiología , Anciano , Adulto , Medición de Riesgo/métodos , Factores de Riesgo de Enfermedad Cardiaca , Factores de Riesgo , Fumar/epidemiología , Factores de Edad , Hipertensión/epidemiología , Factores Sexuales , Presión Sanguínea
14.
Hong Kong Med J ; 30(2): 110-119, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38651202

RESUMEN

INTRODUCTION: Methotrexate (MTX) is effective for treating psoriasis and psoriatic arthritis, but its potential hepatoxicity remains a concern. Liver biopsy, the gold standard for detecting MTX-induced liver injury, is invasive and carries considerable risk. Transient elastography (TE) offers a non-invasive alternative for detecting advanced liver fibrosis. This study investigated the performance of TE in detecting MTX-induced liver fibrosis among Chinese psoriasis patients, compared with liver biopsy. METHODS: This study included adult patients with clinical psoriasis. Liver stiffness measurement using TE was performed in patients receiving MTX. Exclusion criteria were known liver cirrhosis, positive viral hepatitis carrier status, or conditions influencing TE performance. Liver biopsy was performed when liver stiffness was ≥7.1 kilopascals (kPa) or when the total cumulative dose (TCD) of MTX was ≥3.5 g. RESULTS: A total of 228 patients were screened; among 34 patients who met the inclusion criteria, nine (26.5%) had significant liver fibrosis (Roenigk grade ≥3a). The area under the receiver operating characteristic curve was 0.76 (95% confidence interval=0.59-0.93; P=0.021), indicating that TE had satisfactory performance in detecting liver fibrosis. A cut-off value of 7.1 kPa of liver stiffness yielded 100% sensitivity and 68% specificity. Liver fibrosis was not correlated with the TCD of MTX or the duration of MTX use; it was significantly correlated with obesity and diabetes status (body mass index ≥30 kg/m2, waist circumference ≥138 cm, and glycated haemoglobin level ≥7.8%). CONCLUSION: Transient elastography is reliable and superior to the TCD for detecting liver fibrosis in Chinese psoriasis patients receiving MTX. Liver biopsy should be reserved for high-risk patients or patients with liver stiffness ≥11.7 kPa on TE.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Cirrosis Hepática , Metotrexato , Psoriasis , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biopsia , Fármacos Dermatológicos/uso terapéutico , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/administración & dosificación , Pueblos del Este de Asia , Diagnóstico por Imagen de Elasticidad/métodos , Hígado/patología , Hígado/diagnóstico por imagen , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/patología , Metotrexato/efectos adversos , Metotrexato/uso terapéutico , Metotrexato/administración & dosificación , Psoriasis/tratamiento farmacológico , Psoriasis/complicaciones , Psoriasis/patología , Curva ROC
16.
Ann R Coll Surg Engl ; 106(5): 439-445, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38478020

RESUMEN

INTRODUCTION: Accurate risk scoring in emergency general surgery (EGS) is vital for consent and resource allocation. The emergency surgery score (ESS) has been validated as a reliable preoperative predictor of postoperative outcomes in EGS but has been studied only in the US population. Our primary aim was to perform an external validation study of the ESS in a UK population. Our secondary aim was to compare the accuracy of ESS and National Emergency Laparotomy Audit (NELA) scores. METHODS: We conducted an observational cohort study of adult patients undergoing emergency laparotomy over three years in two UK centres. ESS was calculated retrospectively. NELA scores and all other variables were obtained from the prospectively collected Emergency Laparotomy and Laparoscopic Scottish Audit (ELLSA) database. The primary and secondary outcomes were 30-day mortality and postoperative intensive care unit (ICU) admission, respectively. RESULTS: A total of 609 patients were included. Median age was 65 years, 52.7% were female, the overall mortality was 9.9% and 23.8% were admitted to ICU. Both ESS and NELA were equally accurate in predicting 30-day mortality (c-statistic=0.78 (95% confidence interval (CI), 0.71-0.85) for ESS and c-statistic=0.83 (95% CI, 0.77-0.88) for NELA, p=0.196) and predicting postoperative ICU admission (c-statistic=0.76 (95% CI, 0.71-0.81) for ESS and 0.80 (95% CI, 0.76-0.85) for NELA, p=0.092). CONCLUSIONS: In the UK population, ESS and NELA both predict 30-day mortality and ICU admission with no statistically significant difference but with higher c-statistics for NELA score. Both scores have certain advantages, with ESS being validated for a wider range of outcomes.


Asunto(s)
Laparotomía , Humanos , Femenino , Masculino , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Reino Unido/epidemiología , Laparotomía/estadística & datos numéricos , Laparotomía/mortalidad , Medición de Riesgo/métodos , Urgencias Médicas , Unidades de Cuidados Intensivos/estadística & datos numéricos , Adulto , Anciano de 80 o más Años
17.
Rev Sci Instrum ; 95(2)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38341719

RESUMEN

We present an inversion method capable of robustly unfolding MeV x-ray spectra from filter stack spectrometer (FSS) data without requiring an a priori specification of a spectral shape or arbitrary termination of the algorithm. Our inversion method is based upon the perturbative minimization (PM) algorithm, which has previously been shown to be capable of unfolding x-ray transmission data, albeit for a limited regime in which the x-ray mass attenuation coefficient of the filter material increases monotonically with x-ray energy. Our inversion method improves upon the PM algorithm through regular smoothing of the candidate spectrum and by adding stochasticity to the search. With these additions, the inversion method does not require a physics model for an initial guess, fitting, or user-selected termination of the search. Instead, the only assumption made by the inversion method is that the x-ray spectrum should be near a smooth curve. Testing with synthetic data shows that the inversion method can successfully recover the primary large-scale features of MeV x-ray spectra, including the number of x-rays in energy bins of several-MeV widths to within 10%. Fine-scale features, however, are more difficult to recover accurately. Examples of unfolding experimental FSS data obtained at the Texas Petawatt Laser Facility and the OMEGA EP laser facility are also presented.

18.
Med J Malaysia ; 79(1): 15-20, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38287752

RESUMEN

INTRODUCTION: The use of dexamethasone (DXM) has been associated with decreased mortality in the patients with hypoxemia during the coronavirus disease-2019 (COVID-19) pandemic, while the outcomes with methylprednisolone (MTP) have been mixed. This real-life study aimed to evaluate the outcomes of patients with severe respiratory failure due to COVID-19 who were treated with high doses of MTP. MATERIALS AND METHODS: This retrospective cohort study enrolled hospitalised patients between May 2021 and August 2021, aged 18 years and above, with severe respiratory failure defined by a ratio of oxygen saturation to fraction of inspired oxygen (SF ratio) of less than 235. The treatment protocol involved administering high-dose MTP for 3 days, followed by DXM, and the outcomes were compared with those of patients who received DXM alone (total treatment duration of 10 days for both groups). RESULTS: A total of 99 patients were enrolled, with 79 (79.8%) receiving pulse MTP therapy and 20 (20.2%) being treated with DXM only. The SF ratio significantly improved from a mean of 144.49 (±45.16) at baseline to 208 (±85.19) at 72 hours (p < 0.05), with a mean difference of 63.51 (p < 0.001) in patients who received ≤750 mg of MTP. Additionally, in patients who received >750 mg of MTP, the SF ratio improved from a baseline mean of 130.39 (±34.53) to 208.44 (±86.61) at 72 hours (p < 0.05), with a mean difference of 78.05 (p = 0.001). In contrast, patients who received DXM only demonstrated an SF ratio of 132.85 (±44.1) at baseline, which changed minimally to 133.35 (±44.4) at 72 hours (p = 0.33), with a mean difference of 0.50 (p = 0.972). The incidence of nosocomial infection was higher in the MTP group compared with the DXM group (40.5% vs. 35%, p = 0.653), with a relative risk of 1.16 (95% CI: 0.60-2.23). CONCLUSION: MTP did not demonstrate a significant reduction in intubation or intensive care unit admissions. Although a high dose of MTP improved gas exchange in patients with severe and critical COVID-19, it did not provide an overall mortality benefit compared to standard treatment.


Asunto(s)
COVID-19 , Neumonía , Insuficiencia Respiratoria , Humanos , Metilprednisolona , Estudios Retrospectivos , SARS-CoV-2 , Malasia , Tratamiento Farmacológico de COVID-19 , Neumonía/inducido químicamente , Dexametasona/uso terapéutico
19.
Nucleic Acids Res ; 52(5): 2578-2589, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38261972

RESUMEN

The loading of RecA onto ssDNA by RecBCD is an essential step of RecBCD-mediated homologous recombination. RecBCD facilitates RecA-loading onto ssDNA in a χ-dependent manner via its RecB nuclease domain (RecBn). Before recognition of χ, RecBn is sequestered through interactions with RecBCD. It was proposed that upon χ-recognition, RecBn undocks, allowing RecBn to swing out via a contiguous 70 amino acid linker to reveal the RecA-loading surface, and then recruit and load RecA onto ssDNA. We tested this hypothesis by examining the interactions between RecBn (RecB928-1180) and truncated RecBCD (RecB1-927CD) lacking the nuclease domain. The reconstituted complex of RecB1-927CD and RecBn is functional in vitro and in vivo. Our results indicate that despite being covalently severed from RecB1-927CD, RecBn can still load RecA onto ssDNA, establishing that RecBn does not function while only remaining tethered to the RecBCD complex via the linker. Instead, RecBCD undergoes a χ-induced intramolecular rearrangement to reveal the RecA-loading surface.


Asunto(s)
Proteínas de Escherichia coli , Exodesoxirribonucleasa V , Rec A Recombinasas , ADN de Cadena Simple/genética , Endonucleasas/metabolismo , Proteínas de Escherichia coli/metabolismo , Exodesoxirribonucleasa V/metabolismo , Exodesoxirribonucleasas/metabolismo , Rec A Recombinasas/metabolismo
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