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1.
Nucleic Acids Res ; 51(8): 3529-3539, 2023 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-36987860

RESUMEN

Magnesium, the most abundant divalent cation in cells, catalyzes RNA cleavage but also promotes RNA folding. Because folding can protect RNA from cleavage, we predicted a 'Goldilocks landscape', with local maximum in RNA lifetime at Mg2+ concentrations required for folding. Here, we use simulation and experiment to discover an innate and sophisticated mechanism of control of RNA lifetime. By simulation we characterized RNA Goldilocks landscapes and their dependence on cleavage and folding parameters. Experiments with yeast tRNAPhe and the Tetrahymena ribozyme P4-P6 domain show that structured RNAs can inhabit Goldilocks peaks. The Goldilocks peaks are tunable by differences in folded and unfolded cleavage rate constants, Mg2+ binding cooperativity, and Mg2+ affinity. Different folding and cleavage parameters produce Goldilocks landscapes with a variety of features. Goldilocks behavior allows ultrafine control of RNA chemical lifetime, whereas non-folding RNAs do not display Goldilocks peaks of protection. In sum, the effects of Mg2+ on RNA persistence are expected to be pleomorphic, both protecting and degrading RNA. In evolutionary context, Goldilocks behavior may have been a selectable trait of RNA in an early Earth environment containing Mg2+ and other metals.


Asunto(s)
ARN Catalítico , ARN , ARN/química , Magnesio/química , Secuencia de Bases , Conformación de Ácido Nucleico , Cinética , ARN Catalítico/química
2.
Am J Hum Genet ; 106(4): 549-558, 2020 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-32169168

RESUMEN

De novo variants (DNVs) cause many genetic diseases. When DNVs are examined in the whole coding regions of genes in next-generation sequencing analyses, pathogenic DNVs often cluster in a specific region. One such region is the last exon and the last 50 bp of the penultimate exon, where truncating DNVs cause escape from nonsense-mediated mRNA decay [NMD(-) region]. Such variants can have dominant-negative or gain-of-function effects. Here, we first developed a resource of rates of truncating DNVs in NMD(-) regions under the null model of DNVs. Utilizing this resource, we performed enrichment analysis of truncating DNVs in NMD(-) regions in 346 developmental and epileptic encephalopathy (DEE) trios. We observed statistically significant enrichment of truncating DNVs in semaphorin 6B (SEMA6B) (p value: 2.8 × 10-8; exome-wide threshold: 2.5 × 10-6). The initial analysis of the 346 individuals and additional screening of 1,406 and 4,293 independent individuals affected by DEE and developmental disorders collectively identified four truncating DNVs in the SEMA6B NMD(-) region in five individuals who came from unrelated families (p value: 1.9 × 10-13) and consistently showed progressive myoclonic epilepsy. RNA analysis of lymphoblastoid cells established from an affected individual showed that the mutant allele escaped NMD, indicating stable production of the truncated protein. Importantly, heterozygous truncating variants in the NMD(+) region of SEMA6B are observed in general populations, and SEMA6B is most likely loss-of-function tolerant. Zebrafish expressing truncating variants in the NMD(-) region of SEMA6B orthologs displayed defective development of brain neurons and enhanced pentylenetetrazole-induced seizure behavior. In summary, we show that truncating DNVs in the final exon of SEMA6B cause progressive myoclonic epilepsy.


Asunto(s)
Exoma/genética , Exones/genética , Predisposición Genética a la Enfermedad/genética , Variación Genética/genética , Epilepsias Mioclónicas Progresivas/genética , Semaforinas/genética , Adolescente , Adulto , Alelos , Animales , Femenino , Heterocigoto , Humanos , Masculino , Degradación de ARNm Mediada por Codón sin Sentido/genética , Convulsiones/genética , Adulto Joven , Pez Cebra/genética
3.
Malar J ; 22(1): 292, 2023 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-37789320

RESUMEN

BACKGROUND: Since 2018, no indigenous human malaria cases has been reported in Malaysia. However, during the recent COVID-19 pandemic the World Health Organization is concerned that the pandemic might erode the success of malaria control as there are reports of increase malaria cases in resource limited countries. Little is known how the COVID-19 pandemic has impacted malaria in middle-income countries like Malaysia. Here the public health response to a Plasmodium malariae outbreak occurred in a village in Sabah state, Malaysia, during a COVID-19 movement control order is reported. METHODS: An outbreak was declared following the detection of P. malariae in July 2020 and active case detection for malaria was performed by collecting blood samples from residents residing within 2 km radius of Moyog village. Vector prevalence and the efficacy of residual insecticides were determined. Health awareness programmes were implemented to prevent future outbreaks. A survey was conducted among villagers to understand risk behaviour and beliefs concerning malaria. RESULTS: A total of 5254 blood samples collected from 19 villages. Among them, 19 P. malariae cases were identified, including the index case, which originated from a man who returned from Indonesia. His return from Indonesia and healthcare facilities visit coincided with the movement control order during COVID-19 pandemic when the healthcare facilities stretched its capacity and only serious cases were given priority. Despite the index case being a returnee from a malaria endemic area presenting with mild fever, no malaria test was performed at local healthcare facilities. All cases were symptomatic and uncomplicated except for a pregnant woman with severe malaria. There were no deaths; all patients recovered following treatment with artemether-lumefantrine combination therapy. Anopheles balabacensis and Anopheles barbirostris were detected in ponds, puddles and riverbeds. The survey revealed that fishing and hunting during night, and self-treatment for mild symptoms contributed to the outbreak. Despite the index case being a returnee from a malaria-endemic area presenting with mild fever, no malaria test was performed at local healthcare facilities. CONCLUSION: The outbreak occurred during a COVID-19 movement control order, which strained healthcare facilities, prioritizing only serious cases. Healthcare workers need to be more aware of the risk of malaria from individuals who return from malaria endemic areas. To achieve malaria elimination and prevention of disease reintroduction, new strategies that include multisectoral agencies and active community participation are essential for a more sustainable malaria control programme.


Asunto(s)
Anopheles , Antimaláricos , COVID-19 , Malaria , Plasmodium knowlesi , Masculino , Animales , Femenino , Humanos , Malasia/epidemiología , Plasmodium malariae , Salud Pública , Pandemias , Mosquitos Vectores , Arteméter , Combinación Arteméter y Lumefantrina , COVID-19/epidemiología , Malaria/epidemiología , Malaria/prevención & control , Brotes de Enfermedades
4.
Sensors (Basel) ; 23(7)2023 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-37050571

RESUMEN

Several studies have been conducted using both visual and thermal facial images to identify human affective states. Despite the advantages of thermal facial images in recognizing spontaneous human affects, few studies have focused on facial occlusion challenges in thermal images, particularly eyeglasses and facial hair occlusion. As a result, three classification models are proposed in this paper to address the problem of thermal occlusion in facial images, with six basic spontaneous emotions being classified. The first proposed model in this paper is based on six main facial regions, including the forehead, tip of the nose, cheeks, mouth, and chin. The second model deconstructs the six main facial regions into multiple subregions to investigate the efficacy of subregions in recognizing the human affective state. The third proposed model in this paper uses selected facial subregions, free of eyeglasses and facial hair (beard, mustaches). Nine statistical features on apex and onset thermal images are implemented. Furthermore, four feature selection techniques with two classification algorithms are proposed for a further investigation. According to the comparative analysis presented in this paper, the results obtained from the three proposed modalities were promising and comparable to those of other studies.


Asunto(s)
Emociones , Expresión Facial , Humanos , Cara/diagnóstico por imagen , Algoritmos , Boca
5.
Epilepsia ; 63(8): 2011-2023, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35527506

RESUMEN

OBJECTIVE: This study was undertaken to determine the hemoglobin A1c (HbA1c) and modified glucose-ketone index (mGKI) in children on different types of ketogenic diet (KD) for treatment of drug-resistant epilepsy, with attempts to evaluate their relationships with components of diet regime and other biomarkers. METHODS: We conducted a cross-sectional study in children with drug resistant epilepsy aged between 6 months and 18 years, who were on various types of KD therapies without any change in regime for at least 3 months. Parental interview, review of medical records, and a single measurement for blood ketone, HbA1c, and plasma carnitine were performed. mGKI was the ratio of an average plasma glucose estimated from HbA1c to blood ß-hydroxybutyrate level. RESULTS: Thirty-four patients were recruited with a median blood ketone of 2.90 mmol·L-1 and median HbA1c of 4.55%. Those on classical KD (cKD) had higher blood ketone (p = .031) and lower HbA1c (p = .010) and mGKI (p = .021) than those receiving modified Atkins diet, although both shared similar percentages of calories from carbohydrate (p = .211). The cKD and medium-chain triglyceride (MCT) KD groups had similar HbA1c (p = .252) and mGKI (p = .510). Blood ketone (p = .045) and the percentage of calories from MCT (p = .037) were the two main independent variables, inversely correlating with HbA1c. Other than plasma acylcarnitine (p = .047), neither blood ketone (p = .188) nor HbA1c (p = .170) could predict seizure reduction reliably. Both plasma acylcarnitine ≥ 6 µmol·L-1 (p = .013) and mGKI ≤ 2.2 (p = .013) were significantly associated with good seizure control. SIGNIFICANCE: HbA1c could potentially be useful for monitoring KD adherence or, indirectly, systemic ketosis in nondiabetic children on KD for drug-resistant epilepsy. Plasma acylcarnitine and mGKI could be important biomarkers in the management of KD therapy.


Asunto(s)
Dieta Cetogénica , Epilepsia Refractaria , Insuficiencia Renal Crónica , Biomarcadores , Glucemia , Niño , Estudios Transversales , Hemoglobina Glucada , Humanos , Lactante , Cetonas , Convulsiones , Resultado del Tratamiento , Triglicéridos
6.
Int Arch Occup Environ Health ; 95(5): 1113-1127, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35091853

RESUMEN

INTRODUCTION: The implications of work-related stress among manufacturing workers were often unrecognised. The purpose of this study is to determine the effectiveness of the workplace health promotion (WHP) program in reducing depression, anxiety, and stress levels, as well as improving the overall quality of life among Malaysian manufacturing workers. METHODS: The study used a randomised controlled trial (RCT) design and included 88 employees from a food and beverage manufacturing factory in Klang Valley, Malaysia. The intervention group received a comprehensive WHP program based on organisational and individual stress management programs that included (i) healthy mental health module, (ii) anxiety management technique, (iii) mindfulness for stress and (iv) stress at work. The module was delivered through the Occupational Stress Management Course and Employee Assistance Program. The control group received no further intervention other than a general brochure on stress. The study period consisted of an intervention period of 3 months followed by a post-intervention period of 3 months. Measurements were recorded at baseline and at 3 month post-intervention. Outcome measures included the self-perceived depression, anxiety, and stress (DASS-21), participant's quality of life (WHOQOL), coping skills (COPE-28) and job characteristics (JCQ). RESULTS: The intervention group demonstrated a significant reduction in self-perceived stress, anxiety, and depression scores three months post intervention (p ≤ 0.001). All domains of health-related quality of life and coping skills related to social support and problem-solving were significantly improved in the intervention group following the intervention (p < 0.001). In the control group, no significant changes were observed in all the parameters. CONCLUSION: WHP program shows promising results in improving mental health status, quality of life and coping skills among the manufacturing workers.


Asunto(s)
Estrés Laboral , Lugar de Trabajo , Ansiedad/prevención & control , Depresión/prevención & control , Promoción de la Salud , Humanos , Malasia , Estrés Laboral/prevención & control , Estrés Laboral/psicología , Estrés Psicológico/prevención & control , Lugar de Trabajo/psicología
7.
J Pak Med Assoc ; 72(1): 164-167, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35099460

RESUMEN

Cerebral myiasis is extremely rare, and surgical intervention is the primary treatment used. Successful conservative management alone, without surgical removal of the brain infestation has not yet been published. We report a case of a 24-year-old African homeless man who was found on the street in a state of decreased level of consciousness, with larvae exiting from the left supra and postauricular dirty wounds and from his left ear. The patient was diagnosed with post-traumatic cerebral myiasis of the left temporal lobe and cerebellum. It was treated successfully by debridement of the external wounds and administration of antibiotics, without surgical removal of the brain infestations. For the first time, this case illustrates the novelty and appropriateness of the conservative management of cerebral myiasis. This is also the first report of cerebral myiasis with cerebellar involvement and the second report of post-traumatic cerebral myiasis in literature.


Asunto(s)
Tratamiento Conservador , Miasis , Adulto , Animales , Encéfalo , Oído , Humanos , Larva , Masculino , Miasis/diagnóstico , Miasis/terapia , Adulto Joven
8.
Sensors (Basel) ; 21(23)2021 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-34883959

RESUMEN

Three-dimensional reconstruction plays a vital role in assisting doctors and surgeons in diagnosing the healing progress of bone defects. Common three-dimensional reconstruction methods include surface and volume rendering. As the focus is on the shape of the bone, this study omits the volume rendering methods. Many improvements have been made to surface rendering methods like Marching Cubes and Marching Tetrahedra, but not many on working towards real-time or near real-time surface rendering for large medical images and studying the effects of different parameter settings for the improvements. Hence, this study attempts near real-time surface rendering for large medical images. Different parameter values are experimented on to study their effect on reconstruction accuracy, reconstruction and rendering time, and the number of vertices and faces. The proposed improvement involving three-dimensional data smoothing with convolution kernel Gaussian size 5 and mesh simplification reduction factor of 0.1 is the best parameter value combination for achieving a good balance between high reconstruction accuracy, low total execution time, and a low number of vertices and faces. It has successfully increased reconstruction accuracy by 0.0235%, decreased the total execution time by 69.81%, and decreased the number of vertices and faces by 86.57% and 86.61%, respectively.


Asunto(s)
Imagenología Tridimensional , Mallas Quirúrgicas , Algoritmos , Distribución Normal , Prótesis e Implantes
9.
Qatar Med J ; 2021(3): 68, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34926191

RESUMEN

BACKGROUND: Depression and anxiety are major health problems found to be associated with various conditions. COVID-19 is a global pandemic that has a substantial effect on the worldwide population. This study aimed to assess the prevalence of depression and anxiety among male patients with COVID-19 and explore their relationship with participants' characteristics. METHODS: This cross-sectional study was conducted among expatriate male patients with COVID-19 admitted to Lebsayyer Field Hospital in Qatar with mild COVID-19 (according to World Health Organization classification) from July till August 2020. The sample size was calculated using Cochran's formula based on disease prevalence. All eligible patients were invited to participate until reaching 400 participants, who then completed an anonymous survey of sociodemographic questions, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 questionnaire, which are validated screening tools for depression and anxiety, respectively. RESULTS: Of the 400 participants, 148 (37.0%) and 77 (19.3%) reported depressive and anxiety symptoms, respectively. Depression was more prevalent among those 40-49 years old (p = 0.029), while anxiety was more prevalent among people aged  ≥ 50 (p = 0.456). Both depression (p = 0.009) and anxiety (p = 0.042) were more prevalent among Bangladeshi, followed by Filipino participants. Depression was more prevalent among those with the highest income (> 15,000 QR; p = 0.004), in contrast to anxiety, which was more prevalent among those with the lowest monthly income ( <  2,000 QR; p = 0.039). CONCLUSION: The prevalence of depressive and anxiety symptoms is high among the study participants. Associated factors identified by the study were unsteady income, poor self-rated health, living with family, Southeast Asian ethnicity, and age group of 40-49 years.

10.
Ecotoxicol Environ Saf ; 148: 293-302, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29080527

RESUMEN

This study intends to determine the health impacts from two office life cycles (St.1 and St.2) using life cycle assessment (LCA) and health risk assessment of indoor metals in coarse particulates (particulate matter with diameters of less than 10µm). The first building (St.1) is located in the city centre and the second building (St.2) is located within a new development 7km away from the city centre. All life cycle stages are considered and was analysed using SimaPro software. The trace metal concentrations were determined by inductively couple plasma-mass spectrometry (ICP-MS). Particle deposition in the human lung was estimated using the multiple-path particle dosimetry model (MPPD). The results showed that the total human health impact for St.1 (0.027 DALY m-2) was higher than St.2 (0.005 DALY m-2) for a 50-year lifespan, with the highest contribution from the operational phase. The potential health risk to indoor workers was quantified as a hazard quotient (HQ) for non-carcinogenic elements, where the total values for ingestion contact were 4.38E-08 (St.1) and 2.59E-08 (St.2) while for dermal contact the values were 5.12E-09 (St.1) and 2.58E-09 (St.2). For the carcinogenic risk, the values for dermal and ingestion routes for both St.1 and St.2 were lower than the acceptable limit which indicated no carcinogenic risk. Particle deposition for coarse particles in indoor workers was concentrated in the head, followed by the pulmonary region and tracheobronchial tract deposition. The results from this study showed that human health can be significantly affected by all the processes in office building life cycle, thus the minimisation of energy consumption and pollutant exposures are crucially required.


Asunto(s)
Evaluación del Impacto en la Salud , Metales/análisis , Exposición Profesional/análisis , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Polvo/análisis , Monitoreo del Ambiente/métodos , Humanos , Salud Laboral , Tamaño de la Partícula , Material Particulado/química
11.
Environ Monit Assess ; 190(10): 575, 2018 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-30191321

RESUMEN

Malaysia is facing an increasing trend in industrial solid waste generation due to industrial development. Thus, there is a paramount need in taking practical actions and measurements to move toward sustainable industrial waste management. The main aim of this study is to assess practicing solid waste minimization by manufacturing firms. Analysis showed that majority of firms (92%) dispose of their wastes rather than utilize other sustainable waste management options. Also, waste minimization methods such as segregation of wastes, on-site recycle and reuse, improved housekeeping, and equipment modification were found to have significant contribution to waste reduction (p < 0.05). Lack of expertise (M = 3.50), lack of enough information (M = 3.54), lack of equipment modification (M = 3.16), and lack of specific waste minimization guidelines (M = 3.49) have higher mean score comparing with other barriers in different categories. These data were interpreted for elaborating on SWOT and TOWS (strengths, weaknesses, threats, and opportunities) matrix to highlight strengths, weaknesses, threats, and opportunities. Subsequently, ten policies were recommended for improvement of practicing waste minimization by manufacturing firms as the main objective of this research.


Asunto(s)
Monitoreo del Ambiente/métodos , Residuos Industriales/análisis , Eliminación de Residuos/métodos , Residuos Sólidos/análisis , Comercio , Malasia , Políticas , Reciclaje , Administración de Residuos/métodos
12.
J Bacteriol ; 198(6): 964-72, 2016 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-26755631

RESUMEN

UNLABELLED: Urinary tract infection (UTI) is one of the most common ailments requiring both short-term and prophylactic antibiotic therapies. Progression of infection from the bladder to the kidney is associated with more severe clinical symptoms (e.g., fever and vomiting) as well as with dangerous disease sequelae (e.g., renal scaring and sepsis). Host-pathogen interactions that promote bacterial ascent to the kidney are not completely understood. Prior studies indicate that the magnitude of proinflammatory cytokine elicitation in vitro by clinical isolates of uropathogenic Escherichia coli (UPEC) inversely correlates with the severity of clinical disease. Therefore, we hypothesize that the magnitude of initial proinflammatory responses during infection defines the course and severity of disease. Clinical UPEC isolates obtained from patients with a nonfebrile UTI elicited high systemic proinflammatory responses early during experimental UTI in a murine model and were attenuated in bladder and kidney persistence. Conversely, UPEC isolates obtained from patients with febrile UTI elicited low systemic proinflammatory responses early during experimental UTI and exhibited prolonged persistence in the bladder and kidney. Soluble factors in the supernatant from saturated cultures as well as the lipopolysaccharide (LPS) serotype correlated with the magnitude of proinflammatory responses in vitro. Our data suggest that the structure of the O-antigen sugar moiety of the LPS may determine the strength of cytokine induction by epithelial cells. Moreover, the course and severity of disease appear to be the consequence of the magnitude of initial cytokines produced by the bladder epithelium during infection. IMPORTANCE: The specific host-pathogen interactions that determine the extent and course of disease are not completely understood. Our studies demonstrate that modest changes in the magnitude of cytokine production observed using in vitro models of infection translate into significant ramifications for bacterial persistence and disease severity. While many studies have demonstrated that modifications of the LPS lipid A moiety modulate the extent of Toll-like receptor 4 (TLR4) activation, our studies implicate the O-antigen sugar moiety as another potential rheostat for the modulation of proinflammatory cytokine production.


Asunto(s)
Citocinas/metabolismo , Antígenos O/inmunología , Serogrupo , Infecciones Urinarias/inmunología , Infecciones Urinarias/microbiología , Escherichia coli Uropatógena/clasificación , Escherichia coli Uropatógena/inmunología , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Células Epiteliales/inmunología , Células Epiteliales/microbiología , Humanos , Ratones , Antígenos O/clasificación , Sistema Urinario/inmunología , Sistema Urinario/microbiología , Sistema Urinario/patología , Infecciones Urinarias/patología , Escherichia coli Uropatógena/aislamiento & purificación , Escherichia coli Uropatógena/patogenicidad
13.
Infect Immun ; 84(9): 2505-23, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27324481

RESUMEN

Increasing experimental evidence supports the idea that Mycobacterium tuberculosis has evolved strategies to survive within lysosomes of activated macrophages. To further our knowledge of M. tuberculosis response to the hostile lysosomal environment, we profiled the global transcriptional activity of M. tuberculosis when exposed to the lysosomal soluble fraction (SF) prepared from activated macrophages. Transcriptome sequencing (RNA-seq) analysis was performed using various incubation conditions, ranging from noninhibitory to cidal based on the mycobacterial replication or killing profile. Under inhibitory conditions that led to the absence of apparent mycobacterial replication, M. tuberculosis expressed a unique transcriptome with modulation of genes involved in general stress response, metabolic reprogramming, respiration, oxidative stress, dormancy response, and virulence. The transcription pattern also indicates characteristic cell wall remodeling with the possible outcomes of increased infectivity, intrinsic resistance to antibiotics, and subversion of the host immune system. Among the lysosome-specific responses, we identified the glgE-mediated 1,4 α-glucan synthesis pathway and a defined group of VapBC toxin/anti-toxin systems, both of which represent toxicity mechanisms that potentially can be exploited for killing intracellular mycobacteria. A meta-analysis including previously reported transcriptomic studies in macrophage infection and in vitro stress models was conducted to identify overlapping and nonoverlapping pathways. Finally, the Tap efflux pump-encoding gene Rv1258c was selected for validation. An M. tuberculosis ΔRv1258c mutant was constructed and displayed increased susceptibility to killing by lysosomal SF and the antimicrobial peptide LL-37, as well as attenuated survival in primary murine macrophages and human macrophage cell line THP-1.


Asunto(s)
Regulación Bacteriana de la Expresión Génica/genética , Lisosomas/genética , Mycobacterium tuberculosis/genética , Estrés Oxidativo/genética , Transcripción Genética/genética , Animales , Péptidos Catiónicos Antimicrobianos , Catelicidinas/genética , Línea Celular , Interacciones Huésped-Patógeno/genética , Humanos , Macrófagos/microbiología , Ratones , Ratones Endogámicos BALB C , Transcriptoma/genética , Tuberculosis/microbiología , Virulencia/genética
14.
Epilepsia ; 57(8): 1271-9, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27378185

RESUMEN

OBJECTIVE: Long-term use of antiepileptic drugs (AEDs) is a significant risk factor for vitamin D deficiency in children with epilepsy. The aims of our study were to evaluate the prevalence and risk factors for vitamin D deficiency among Malaysian children with epilepsy. METHODS: Cross-sectional study of ambulant children with epilepsy on long-term AEDs for >1 year seen in three tertiary hospitals in Malaysia from April 2014 to April 2015. Detailed assessment of pubertal status, skin pigmentation, sunshine exposure behavior, physical activity, dietary vitamin D and calcium intake, anthropometric measurements and bone health blood tests (vitamin D, alkaline phosphatase, calcium, phosphate, and parathyroid hormone levels) were obtained on all patients. Vitamin D deficiency was defined as 25-hydroxy vitamin D [25(OH)D] levels ≤35 nmol/L and insufficiency as 25(OH)D levels of 36-50 nmol/L. RESULTS: A total of 244 children (146 male) participated in the study. Ages ranged between 3.7 and 18.8 years (mean 12.3 years). 25(OH)D levels ranged between 7.5 and 140.9 nmol/L (mean 53.9 nmol/L). Vitamin D deficiency was identified in 55 patients (22.5%), and a further 48 (19.7%) had vitamin D insufficiency. Multivariate logistic regression analysis identified polytherapy >1 AED (odds ratio [OR] 2.16, 95% confidence interval [CI] 1.07-4.36), age >12 years (OR 4.16, 95% CI 1.13-15.30), Indian ethnicity (OR 6.97, 95% CI 2.48-19.55), sun exposure time 30-60 min/day (OR 2.44, 95% CI 1.05-5.67), sun exposure time <30 min/day (OR 3.83, 95% CI 1.61-9.09), and female (OR 2.61, 95% CI 1.31-5.20) as statistically significant (p < 0.05) risk factors for vitamin D deficiency. SIGNIFICANCE: Despite living in the tropics, a high proportion of Malaysian children with epilepsy are at risk of vitamin D deficiency. Targeted strategies including vitamin D supplementation and lifestyle advice of healthy sunlight exposure behavior should be implemented among children with epilepsy, particularly for those at high risk of having vitamin D deficiency.


Asunto(s)
Anticonvulsivantes/efectos adversos , Epilepsia/epidemiología , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/etiología , Adolescente , Factores de Edad , Antropometría , Niño , Preescolar , Estudios Transversales , Epilepsia/tratamiento farmacológico , Femenino , Humanos , Malasia/epidemiología , Masculino , Prevalencia , Factores de Riesgo , Luz Solar , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/diagnóstico , Adulto Joven
15.
Pediatr Res ; 80(4): 602-9, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27384406

RESUMEN

BACKGROUND: Congenital obstructive nephropathy (CON) is a leading cause of pediatric chronic kidney disease (CKD). Despite optimal surgical and medical care, there is a high rate of CKD progression. Better understanding of molecular and cellular changes is needed to facilitate development of improved biomarkers and novel therapeutic approaches in CON. METHODS: The megabladder (mgb) mouse is an animal model of CKD with impaired bladder emptying, hydronephrosis, and progressive renal injury. In this study, we characterize a particular microRNA, miR-205, whose expression changes with the degree of hydronephrosis in the mgb(-/-) kidney. RESULTS: Expression of miR-205 is progressively increased in the adult mgb(-/-) mouse with worsening severity of hydronephrosis. miR-205 expression is correlated with altered expression of cytokeratins and uroplakins, which are markers of cellular differentiation in urothelium. We describe the spatial pattern of miR-205 expression, including increased expression in renal urothelium and novel miR-205 expression in medullary collecting duct epithelium in the congenitally obstructed kidney. CONCLUSION: miR-205 is increased with severity of CON and CKD in the mgb(-/-) mouse and may regulate urothelial differentiation.


Asunto(s)
Epitelio/metabolismo , Regulación de la Expresión Génica , Enfermedades Renales/congénito , MicroARNs/genética , Animales , Biomarcadores/sangre , Biomarcadores/metabolismo , Diferenciación Celular , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Hidronefrosis/sangre , Queratinas/sangre , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/genética , Enfermedades Renales/fisiopatología , Fallo Renal Crónico/sangre , Túbulos Renales Colectores/metabolismo , Masculino , Ratones , Ratones Transgénicos , Uniones Estrechas , Uroplaquinas/sangre , Urotelio/metabolismo , Urotelio/patología
16.
BMC Cancer ; 14: 212, 2014 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-24650245

RESUMEN

BACKGROUND: Cancer is the leading cause of deaths in the world. A widening disparity in cancer burden has emerged between high income and low-middle income countries. Closing this cancer divide is an ethical imperative but there is a dearth of data on cancer services from developing countries. METHODS: This was a multi-center, retrospective observational cohort study which enrolled women with breast cancer (BC) attending 8 participating cancer centers in Malaysia in 2011. All patients were followed up for 12 months from diagnosis to determine their access to therapies. We assess care performance using measures developed by Quality Oncology Practice Initiative, American Society of Clinical Oncology/National Comprehensive Cancer Network, American College of Surgeons' National Accreditation Program for Breast Centers as well as our local guideline. RESULTS: Seven hundred and fifty seven patients were included in the study; they represent about 20% of incident BC in Malaysia. Performance results were mixed. Late presentation was 40%. Access to diagnostic and breast surgery services were timely; the interval from presentation to tissue diagnosis was short (median = 9 days), and all who needed surgery could receive it with only a short wait (median = 11 days). Performance of radiation, chemo and hormonal therapy services showed that about 75 to 80% of patients could access these treatments timely, and those who could not were because they sought alternative treatment or they refused treatment. Access to Trastuzumab was limited to only 19% of eligible patients. CONCLUSIONS: These performance results are probably acceptable for a middle income country though far below the 95% or higher adherence rates routinely reported by centres in developed countries. High cost trastuzumab was inaccessible to this population without public funding support.


Asunto(s)
Neoplasias de la Mama/economía , Neoplasias de la Mama/epidemiología , Países en Desarrollo/economía , Salud Global/economía , Accesibilidad a los Servicios de Salud/economía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico , Estudios de Cohortes , Femenino , Humanos , Malasia/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
17.
Carbohydr Polym ; 338: 122199, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38763725

RESUMEN

Deep eutectic solvents (DES) emerge as promising alternatives to conventional solvents, offering outstanding extraction capabilities, low toxicity, eco-friendliness, straightforward synthesis procedures, broad applicability, and impressive recyclability. DES are synthesized by combining two or more components through various synthesis procedures, such as heat-assisted mixing/stirring, grinding, freeze drying, and evaporation. Polysaccharides, as abundant natural materials, are highly valued for their biocompatibility, biodegradability, and sustainability. These versatile biopolymers can be derived from various natural sources such as plants, algae, animals, or microorganisms using diverse extraction techniques. This review explores the synthesis procedures of DES, their physicochemical properties, characterization analysis, and their application in polysaccharide extraction. The extraction optimization strategies, parameters affecting DES-based polysaccharide extraction, and separation mechanisms are comprehensively discussed. Additionally, this review provides insights into recently developed molecular guides for DES screening and the utilization of artificial neural networks for optimizing DES-based extraction processes. DES serve as excellent extraction media for polysaccharides from different sources, preserving their functional features. They are utilized both as extraction solvents and as supporting media to enhance the extraction abilities of other solvents. Continued research aims to improve DES-based extraction methods and achieve selective, energy-efficient processes to meet the demands of this expanding field.


Asunto(s)
Disolventes Eutécticos Profundos , Polisacáridos , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Disolventes Eutécticos Profundos/química , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Animales , Solventes/química , Fraccionamiento Químico/métodos , Plantas/química
18.
Environ Anal Health Toxicol ; 39(1): e2024010-0, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38631402

RESUMEN

The repercussions of climate change have profound implications for human health, leading to the emergence of climate-related diseases. Recognizing this, the Ministry of Environment and Forestry in Indonesia has established the Climate Village Program to tackle and mitigate the impact of climate change. Despite the implementation of this program, Larangan Village in Candi Sub-district, Sidoarjo Regency, continues to struggle with cases of climate-related diseases. This research aims to assess the impact of waste management on the prevalence of climate-related diseases in Larangan Village. Using a quantitative, analytical, observational approach with a cross-sectional design, the study concentrates on two neighborhoods within Larangan Village. The population consists of 330 families in the 2nd neighborhood (Non-Climate Village Program) and 344 families in the 9th neighborhood (Climate Village Program), with a sample size of 109. The variables under investigation encompass waste management and climate-related diseases. Data collection involves conducting interviews and distributing questionnaires among community members in both neighborhoods. The collected data undergo analysis using Multigroup Analysis SEM PLS with a significance level of 0.05. The findings reveal a significant negative correlation between waste management and climate-related diseases, suggesting that enhanced waste management is linked to a reduced incidence of such diseases in the community.

19.
Neurol Neuroimmunol Neuroinflamm ; 11(1): e200186, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38086061

RESUMEN

BACKGROUND AND OBJECTIVES: We characterize clinical and neuroimaging features of SARS-CoV-2-related acute necrotizing encephalopathy (ANE). METHODS: Systematic review of English language publications in PubMed and reference lists between January 1, 2020, and June 30, 2023, in accordance with PRISMA guidelines. Patients with SARS-CoV-2 infection who fulfilled diagnostic criteria for sporadic and genetic ANE were included. RESULTS: From 899 articles, 20 cases (17 single case reports and 3 additional cases) were curated for review (50% female; 8 were children). Associated COVID-19 illnesses were febrile upper respiratory tract infections in children while adults had pneumonia (45.6%) and myocarditis (8.2%). Children had early neurologic deterioration (median day 2 in children vs day 4 in adults), seizures (5 (62.5%) children vs 3 of 9 (33.3%) adults), and motor abnormalities (6 of 7 (85.7%) children vs 3 of 7 (42.9%) adults). Eight of 12 (66.7%) adults and 4 (50.0%) children had high-risk ANE scores. Five (62.5%) children and 12 (66.7%) adults had brain lesions bilaterally and symmetrically in the putamina, external capsules, insula cortex, or medial temporal lobes, in addition to typical thalamic lesions of ANE. Hypotension was only seen in adults (30%). Hematologic derangements were common: lymphopenia (66.7%), coagulopathy (60.0%), or elevated D-dimers (100%), C-reactive protein (91.7%), and ferritin (62.5%). A pathogenic heterozygous c/.1754 C>T variant in RANBP2 was present in 2 children: one known to have this before SARS-CoV-2 infection, and a patient tested because the SARS-CoV-2 infection was the second encephalopathic illness. Three other children with no prior encephalopathy or family history of encephalopathy were negative for this variant. Fifteen (75%) received immunotherapy (with IV methylprednisolone, immunoglobulins, tocilizumab, or plasma exchange): 6 (40.0%) with monotherapy and 9 (60.0%) had combination therapy. Deaths were in 8 of 17 with data (47.1%): a 2-month-old male infant and 7 adults (87.5%) of median age 56 years (33-70 years), 4 of whom did not receive immunotherapy. DISCUSSION: Children and adults with SARS-CoV-2 ANE have similar clinical features and neuroimaging characteristics. Mortality is high, predominantly in patients not receiving immunotherapy and at the extremes of age.


Asunto(s)
Encefalopatías , COVID-19 , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Encefalopatías/diagnóstico por imagen , COVID-19/complicaciones , Metilprednisolona , SARS-CoV-2 , Convulsiones , Anciano
20.
Rheumatol Int ; 33(6): 1637-42, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22202921

RESUMEN

The purpose of this study is to determine the ocular manifestations of systemic lupus erythematosus and its correlation with the disease activity. Fifty-two lupus patients and 20 healthy controls were included in this study. All patients have undergone complete rheumatological, neurological, and ophthalmic examination including visual acuity, slit-lamp examination of the anterior segment, and dry eye evaluation using Rose Bengal stain and Schirmer test. Fundus examination and fundus photography were done to the suspected cases. Eighteen patients (34.6%) had ocular lesion, from which only 13 (25%) patients were symptomatic. Keratoconjunctivitis was the most common ocular lesion. There was a highly statistically significant difference between patients and controls as regarding all ocular lesions (P > 0.0001). There was good correlation between disease activity index and presence of ocular lesion. Ocular manifestations are common in SLE patients. Lupus retinopathy may reflect systemic, particularly CNS, vascular damage.


Asunto(s)
Oftalmopatías/epidemiología , Lupus Eritematoso Sistémico/complicaciones , Adolescente , Adulto , Femenino , Humanos , Queratoconjuntivitis/epidemiología , Masculino , Persona de Mediana Edad
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