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BACKGROUND: Blunt aortic injury (BAI) and traumatic brain injury (TBI) are the leading causes of death after blunt trauma. The purposes of this study were to identify predictors of mortality for BAI and to examine the impact of procedural heparinization during thoracic endovascular aortic repair (TEVAR) on neurologic outcomes in patients with BAI/TBI. METHODS: Patients with BAI were identified over an 8 year period. Age, gender, severity of injury and shock, time to TEVAR, morbidity, and mortality were recorded and compared. Multivariable logistic regression (MLR) was performed to determine independent predictors of mortality. Youden's index determined optimal time to TEVAR. RESULTS: A total of 129 patients were identified. The majority (74%) were male with a median age and injury severity score (ISS) of 40 years and 29, respectively. Of these, 26 (20%) had a concomitant TBI. Patients with BAI/TBI had higher injury burden at presentation (ISS 37 vs. 29, P = 0.002; Glasgow Coma Scale [GCS] 6 vs. 15, P < 0.0001), underwent fewer TEVAR procedures (31 vs. 53%, P = 0.039), and suffered increased mortality (39 vs. 16%, P = 0.009). All TEVARs had procedural anticoagulation, including patients with TBI, without change in neurologic function. The optimal time to TEVAR was 14.8 hr. Mortality increased in TEVAR patients before 14.8 hr (8.7 vs. 0%, P = 0.210). MLR identified TEVAR as the only modifiable factor that reduced mortality (odds ratio 0.11; 95% confidence interval 0.03-0.45, P = 0.002). CONCLUSIONS: TEVAR use was identified as the only modifiable predictor of reduced mortality in patients with BAI. Delayed TEVAR with the use of procedural heparin provides a safe option regardless of TBI with improved survival and no difference in discharge neurologic function.
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Enfermedades de la Aorta , Procedimientos Endovasculares , Lesiones del Sistema Vascular , Heridas no Penetrantes , Anticoagulantes/efectos adversos , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/lesiones , Aorta Torácica/cirugía , Enfermedades de la Aorta/etiología , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Lesiones del Sistema Vascular/complicaciones , Lesiones del Sistema Vascular/diagnóstico por imagen , Lesiones del Sistema Vascular/cirugía , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/diagnóstico por imagen , Heridas no Penetrantes/cirugíaRESUMEN
Cystic echinococcosis (CE) is a zoonotic disease caused by the larval stage of Echinococcus granulosus tapeworms. These parasites have a worldwide geographic distribution and pose a serious threat to livestock industry as well as human health in the endemic areas. CE is widely distributed in Pakistan. However, very few reports are available related to the regional transmission of E. granulosus. A retrospective analysis was conducted of surgically confirmed CE patients who were treated at Shoukat Khanum Memorial Cancer Hospital and Research Centre in Lahore, Punjab Province, Pakistan from 2007 - 2018. In total, 536 CE patients were evaluated during the study period. Cases originated from the provinces of Khyber Pakhtunkhwa (n=336), Punjab (n=147), Baluchistan (n=18), Sindh (n=3), Islamabad (n=2), Gilgit Baltistan (n=1), and Azad Jammu and Kashmir (n=1). An additional 28 cases were from Afghanistan. The highest number of CE cases was reported in 2013 (n=90). Females made up a larger proportion of cases (n=310; 57.8 %) than males (n=226; 42.2 %). Most patients were members of the Pashtun (n=197; 36.7 %), Hindku (n=142; 26.5 %), and Punjabi (n=118; 22.0 %) ethnic groups. The largest number of cysts was obtained from the liver (137/536; 25.6 %). This study showed that CE is likely present throughout Pakistan. In order to control the disease, a comprehensive control program and regional surveillance are needed.
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OBJECTIVE: To observe the role of motorcycles in causing Road Traffic Accidents and assess the demographics of the drivers, the injury patterns and their outcomes. METHODS: This prospective observational study was conducted at the Surgical Unit 1, Lahore General Hospital, Lahore for a period of 6 months from November 2017 to May 2018. All patients presenting in ER with RTA secondary to motorcycle trauma were included in the study. Data of patients including demographic and medical data, helmet use, spectrum of injuries, specific injury diagnosis, and final disposition of patients was analyzed. The distribution and associations of both victim- and crash-related variables such as crash mechanism, types of involved vehicles, types of injuries, and demographic characteristics were investigated. Data were analyzed by SPSS v23. RESULTS: A total of 835 patients were included in this study with 685 (82%) being male (mean age 28.38 ± 13.89 years) and775 (92.7%) were motorcycle users. The majority of road traffic crashes, traffic accident's mechanism were motorcycle-vehicle accident 579 (69.3%), followed by collision with slow moving carts and bicycles 104 (12.5%). Inner city main roads were the site for 563 (67.4%) accidents. Only 168 (2.2%) patients were wearing helmets at the time of trauma. CONCLUSIONS: Motorcycle traffic morbidities and mortalities remain to be a major public health issue in Lahore as well as all over Pakistan. There is an urgent need for an efficacious interventional programs to decline the burden of motorcycle related morbidity and mortalities.
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Accidentes de Tránsito/estadística & datos numéricos , Motocicletas , Heridas y Lesiones/epidemiología , Traumatismos Abdominales/epidemiología , Traumatismos Abdominales/terapia , Adolescente , Adulto , Traumatismos Craneocerebrales/epidemiología , Traumatismos Craneocerebrales/terapia , Traumatismos Faciales/epidemiología , Traumatismos Faciales/terapia , Femenino , Fracturas Óseas/epidemiología , Fracturas Óseas/cirugía , Dispositivos de Protección de la Cabeza/estadística & datos numéricos , Humanos , Laceraciones/epidemiología , Laceraciones/terapia , Hígado/lesiones , Extremidad Inferior/lesiones , Lesión Pulmonar/epidemiología , Lesión Pulmonar/terapia , Masculino , Pakistán/epidemiología , Estudios Prospectivos , Bazo/lesiones , Traumatismos Torácicos/epidemiología , Traumatismos Torácicos/terapia , Centros Traumatológicos , Extremidad Superior/lesiones , Lesiones del Sistema Vascular/epidemiología , Lesiones del Sistema Vascular/cirugía , Heridas y Lesiones/terapia , Adulto JovenRESUMEN
PURPOSE OF REVIEW: The last 40 years of clinical research in interventional cardiology were extraordinarily innovative. This article will review the most promising up and coming interventional cardiovascular therapies, with a primary focus on the treatment of coronary artery disease. RECENT FINDINGS: From the first stent, to the first transcatheter aortic valve implantation (TAVI), and the left appendage closure technique, percutaneous interventions revolutionized the treatment of multiple diseases and dramatically improved the prognosis of many patients. While these advances have decreased the risk of mortality in some patients (such as ST-elevation myocardial infarction), 15% of acute coronary syndrome (ACS) patients still experience recurrent ischemic events within the first year, challenging us to develop new pharmaceutical targets and new devices. The continued emergence of data supporting inflammation as a risk factor and pharmacologic target as well as data supporting the importance of cholesterol efflux have identified novel therapeutic targets that may play a major role in the improvement of prognosis of patients with coronary artery disease. In addition, novel medical devices are being developed to allow even earlier detection of acute cardiac events and to support high-risk percutaneous coronary interventions. Advances in computing and the ability to analyze large datasets will allow us to use artificial intelligence to augment the clinician patient experience, both in and out of the catheterization laboratory, with live procedural guidance as well as pre- and post-operative prognostication tools.
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Cateterismo Cardíaco , Cardiología , Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Cardiología/tendencias , Enfermedad de la Arteria Coronaria/terapia , Humanos , Sistema de RegistrosRESUMEN
Hepatocellular carcinoma is emerging as one of the most common forms of cancer resulting in thousands of death worldwide. The purpose of this study was to screen nimesulide for anticancer activity in chemically induced hepatocellular carcinoma in Wistar rats as well as in BEL 7402 and HEP G2 cell lines. HCC in rats was induced by administering a single dose of diethyl nitrosamine (150 mg/kg) intraperitoneally. Duration of the in vivo study was 12 weeks and the anticancer potential was further confirmed by in vitro cell line study. Administration of DENA in Wistar rats significantly elevated the levels of serum biochemical parameters and α-feto protein. Treatment with different dose of nimesulide significantly decreased the markedly raised serum levels of biochemical parameters as well as maintained the histology of the liver tissues nearly similar to the normal. Further study of hepatocytes enzymes showed that treatment with nimesulide also improved the antioxidant enzyme levels. Our study also examined the cytotoxicity and DNA synthesis inhibition by nimesulide in BEL 7402 and Hep G2 cell lines. Cell viability was assessed by [3H]-thymidine uptake procedure. The results obtained by in vitro cell line study, histopathological and biochemical data concluded that nimesulide, a preferential COX-2 inhibitor, has anticancer activity, which is by first reducing the formation of reactive oxygen species and second by inhibiting the PGE2 effect via Wnt signaling pathway (cell invasion, angiogenesis, and cell proliferation).
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Antineoplásicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , ADN/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Sulfonamidas/farmacología , Animales , Antioxidantes/farmacología , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Femenino , Células Hep G2 , Humanos , Hígado/efectos de los fármacos , Hígado/metabolismo , Neoplasias Hepáticas/metabolismo , Masculino , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: The dental graduation program is stressful and challenging as it is essential to master various skills. The emotional intelligence (EI) is reported to help in perceiving, moderating emotions and also play a significant role in academic excellence. AIM: The aim of this study was to assess the sociodemographic factors influencing EI and to determine the association of EI in academic performance of clinical and preclinical courses. MATERIALS AND METHODS: This cross-sectional study included the 113 dental clinical internship students from five different dental schools at Pakistan. The self-administered questionnaire data included sociodemographic factors, academic performance in preclinical, clinical courses, and San Diego City College MESA Program-based EI responses. The results were analyzed with multiple linear regression and ordinal regression to identify the independent predictor for EI and academic performance. RESULTS: The female participants had marginally higher mean EI score (109.67) in comparison to male counterparts (108.10). The independent predictors among sociodemographic factors for EI were having siblings (P = 0.016), loss of parents (P = 0.002), parents' education (P = 0.022), and relation with parents (P = 0.03). The students enjoy studying dentistry were also associated with higher EI scores (P = 0.002). The mean EI score was an independent predictor of academic performance predominantly in clinical courses [ß = -0.041 (95% confidence interval - 0.063 to - 0.020); P = 0.000]. CONCLUSION: The finding of the study indicates the influence of family and social factors in the development of EI. The dental students' EI is vital for higher academic performance in clinical courses.
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Rendimiento Académico , Educación en Odontología , Inteligencia Emocional , Emociones , Factores Socioeconómicos , Estudiantes de Odontología/psicología , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Pakistán , Facultades de Odontología , Encuestas y Cuestionarios , UniversidadesRESUMEN
BACKGROUND: The aim was to carry out phase 4 international field-testing of the European Organisation for Research and Treatment of Cancer (EORTC) breast reconstruction (BRECON) module. The primary objective was finalization of its scale structure. Secondary objectives were evaluation of its reliability, validity, responsiveness, acceptability and interpretability in patients with breast cancer undergoing mastectomy and reconstruction. METHODS: The EORTC module development guidelines were followed. Patients were recruited from 28 centres in seven countries. A prospective cohort completed the QLQ-BRECON15 before mastectomy and the QLQ-BRECON24 at 4-8 months after reconstruction. The cross-sectional cohort completed the QLQ-BRECON24 at 1-5 years after reconstruction, and repeated this 2-8 weeks later (test-retest reliability). All participants completed debriefing questionnaires. RESULTS: A total of 438 patients were recruited, 234 in the prospective cohort and 204 in the cross-sectional cohort. A total of 414 reconstructions were immediate, with a comparable number of implants (176) and donor-site flaps (166). Control groups comprised patients who underwent two-stage implant procedures (72, 75 per cent) or delayed reconstruction (24, 25 per cent). Psychometric scale validity was supported by moderate to high item-own scale and item-total correlations (over 0·5). Questionnaire validity was confirmed by good scale-to-sample targeting, and computable scale scores exceeding 50 per cent, except nipple cosmesis (over 40 per cent). In known-group comparisons, QLQ-BRECON24 scales and items differentiated between patient groups defined by clinical criteria, such as type and timing of reconstruction, postmastectomy radiotherapy and surgical complications, with moderate effect sizes. Prospectively, sexuality and surgical side-effects scales showed significant responsiveness over time (P < 0·001). Scale reliability was supported by high Cronbach's α coefficients (over 0·7) and test-retest (intraclass correlation more than 0·8). One item (finding a well fitting bra) was excluded based on high floor/ceiling effects, poor test-retest and weak correlations in factor analysis (below 0·3), thus generating the QLQ-BRECON23 questionnaire. CONCLUSION: The QLQ-BRECON23 is an internationally validated tool to be used alongside the EORTC QLQ-C30 (cancer) and QLQ-BR23 (breast cancer) questionnaires for evaluating quality of life and satisfaction after breast reconstruction.
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Indicadores de Salud , Mamoplastia , Calidad de Vida , Adulto , Anciano , Estudios Transversales , Europa (Continente) , Femenino , Humanos , Mastectomía , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Satisfacción del Paciente , Estudios Prospectivos , Psicometría , Reproducibilidad de los ResultadosRESUMEN
The current study was designed to evaluate bioactive compounds under the influence of biotic stress on seedlings of Peganum harmala. Biologically active compounds were determined by using different techniques. The HPLC and GC-MS analyses detected the significant amount of phenolic acids and active biological compound. Total protein content, activity of proteases, α-amylases, catalases and peroxidases were observed to be accelerated under fungal stress. The seedling extracts exhibited prominent antifungal and antimicrobial activity against selected strains. The present study showed that P. harmala is a good candidate to be used in natural therapies and medicine.
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Antibacterianos/farmacología , Peganum/química , Fitoquímicos/farmacología , Extractos Vegetales/farmacologíaRESUMEN
Short interfering RNAs (siRNAs) are mediators of RNA interference (RNAi), a commonly used technique for selective down-regulation of target gene expression. Using an equimolar mixture of A, G, C, and U phosphoramidites during solid-phase synthesis, we introduced degenerate positions into RNA guide and passenger strands so that, when annealed, a large pool of distinct siRNA duplexes with randomized base pairs at defined sites was created. We assessed the randomization efficiency by deep sequencing one of the RNAs. All possible individual sequences were present in the pool with generally an excellent distribution of bases. Melting temperature analyses suggested that pools of randomized guide and passenger strands RNAs with up to eight degenerate positions annealed so that mismatched base-pairing was minimized. Transfections of randomized siRNAs (rnd-siRNAs) into cells led to inhibition of luciferase reporters by a miRNA-like mechanism when the seed regions of rnd-siRNA guide strands were devoid of degenerate positions. Furthermore, the mRNA levels of a select set of genes associated with siRNA off-target effects were measured and indicated that rnd-siRNAs with degenerate positions in the seed likely show typical non-sequence-specific effects, but not miRNA-like off-target effects. In the wake of recent reports showing the preponderance of miRNA-like off-target effects of siRNAs, our findings are of value for the design of a novel class of easily prepared and universally applicable negative siRNA controls.
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Técnicas de Silenciamiento del Gen/métodos , Interferencia de ARN , ARN Bicatenario/genética , Emparejamiento Base , Secuencia de Bases , Expresión Génica , Células HeLa , Humanos , ARN Interferente Pequeño/genética , TransfecciónRESUMEN
In northern Pakistan, many farming communities rely on domestic yak (Bos grunniens) as a principle source of income. A 2006 participatory disease surveillance report from this region indicated that foot-and-mouth disease (FMD) is the most prevalent annual disease of yak. Our objectives of this study were to determine exposure levels of yak to FMD virus; implement a vaccination program based on current, regional FMD virus serotypes and subtypes; and quantify immune responses following vaccination. Blood samples were used to determine pre-vaccination exposure of animals to FMD virus by antibody presence to non-structural proteins of FMD virus using a 3-ABC trapping indirect ELISA. Vaccine used consisted of FMD serotypes 'O' (PanAsia-2), 'A' (Iran-05), and 'Asia-1' (Shamir), but changed later during the study to match newly circulating viruses in the country ('O'-PanAsia-2; 'A'-Turk-06 and Asia-1-Sindh-08). Three hundred sixty-three blood samples were tested from selected villages to determine pre-vaccination FMD virus exposure in yak with an average of 37.7%. Immune responses from initial vaccination and booster dose 30 days later showed clear protective levels (as mean percent inhibition) of antibodies against structural proteins of serotypes 'O,' 'A,' and 'Asia-1.' These responses remained above threshold positive level even at day 210 following initial vaccination. Results of sero-surveillance and anecdotal information of repeated FMD outbreaks demonstrate the persistence of FMD virus of yak in northern Pakistan. Laboratory results and field observations clearly indicated that yak can be protected against FMD with a good quality vaccine with FMD serotype(s) matching current, regionally circulating FMD virus.
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Bovinos/inmunología , Virus de la Fiebre Aftosa/inmunología , Fiebre Aftosa/prevención & control , Vacunación/estadística & datos numéricos , Animales , Anticuerpos Antivirales , Brotes de Enfermedades/prevención & control , Ensayo de Inmunoadsorción Enzimática , Fiebre Aftosa/epidemiología , Pakistán/epidemiologíaRESUMEN
Functional microRNAs (miRNAs) are produced from both arms of their precursors (pre-miRNAs). Their abundances vary in context-dependent fashion spatiotemporarily and there is mounting evidence of regulatory interplay between them. Here, we introduce chemically synthesized pre-miRNAs (syn-pre-miRNAs) as a general class of accessible, easily transfectable mimics of pre-miRNAs. These are RNA hairpins, identical in sequence to natural pre-miRNAs. They differ from commercially available miRNA mimics through their complete hairpin structure, including any regulatory elements in their terminal-loop regions and their potential to introduce both strands into RISC. They are distinguished from transcribed pre-miRNAs by their terminal 5' hydroxyl groups and their precisely defined terminal nucleotides. We demonstrate with several examples how they fully recapitulate the properties of pre-miRNAs, including their processing by Dicer into functionally active 5p; and 3p-derived mature miRNAs. We use syn-pre-miRNAs to show that miR-34a uses its 5p and 3p miRNAs in two pathways: apoptosis during TGF-ß signaling, where SIRT1 and SP4 are suppressed by miR-34a-5p and miR-34a-3p, respectively; and the lipopolysaccharide (LPS)-activation of primary human monocyte-derived macrophages, where TNF (TNFα) is suppressed by miR-34a-5p indirectly and miR-34a-3p directly. Our results add to growing evidence that the use of both arms of a miRNA may be a widely used mechanism. We further suggest that syn-pre-miRNAs are ideal and affordable tools to investigate these mechanisms.
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Regulación de la Expresión Génica , MicroARNs/fisiología , ARN Bicatenario/fisiología , Factor de Necrosis Tumoral alfa/genética , Apoptosis/efectos de los fármacos , Apoptosis/genética , Células Cultivadas , Células HeLa , Humanos , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , MicroARNs/síntesis química , Precursores del ARN/síntesis química , Precursores del ARN/fisiología , ARN Bicatenario/síntesis química , ARN Interferente Pequeño/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Factor de Crecimiento Transformador beta/farmacologíaRESUMEN
BACKGROUND: The aim of this study was to estimate the impact 2 and 3 years after surgery of implant-assisted latissimus dorsi (LDI) and autologous latissimus dorsi (ALD) flap breast reconstructions on patient-reported outcomes (PROs), and, secondarily, to determine whether baseline characteristics can predict PROs. METHODS: This was a multicentre prospective cohort study. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) and breast cancer module (QLQ-BR23), Functional Assessment of Cancer Therapy - Breast (FACT-B), and Hospital Anxiety and Depression Scale (HADS) PROs were completed before surgery and at 2 and 3 years after breast reconstruction. The effects of LDI and ALD, adjusted for baseline clinicodemographic characteristics, were estimated with multiple linear regressions. Effect sizes above 0·5 were considered clinically important. RESULTS: Some 206 patients (LDI 93, ALD 113) were recruited in 2007-2013; 66·5 per cent were node-negative and 34·6 per cent received radiotherapy. Women with adverse clinicopathological factors were more likely to have received radiotherapy and to undergo ALD. Patients in both surgical groups showed clinically important effects at 2 and 3 years, including improvements in emotional scales, but worse physical functioning, social well-being, body image and anxiety. Radiotherapy adversely affected social functioning at 2 years (P = 0·002). Women undergoing ALD reconstruction had significantly improved sexual functioning at 3 years (P = 0·003) relative to those who had LDI procedures, even after adjusting for case mix (P = 0·007). At 3 years, younger women experienced worse physical well-being than older women (P = 0·006), and chemotherapy was associated with worse arm symptoms (P = 0·005). CONCLUSION: Clinically important changes occurred in physical functioning, breast symptoms, body image and psychological distress. These results will guide selections of key PRO domains and sample-size calculation of future studies.
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Neoplasias de la Mama/cirugía , Mamoplastia/métodos , Evaluación del Resultado de la Atención al Paciente , Músculos Superficiales de la Espalda/cirugía , Colgajos Quirúrgicos , Adulto , Anciano , Neoplasias de la Mama/terapia , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Modelos Lineales , Persona de Mediana Edad , Estudios Prospectivos , Radioterapia AdyuvanteRESUMEN
The black cumin or Nigella sativa L. seeds have many acclaimed medicinal properties such as bronchodilatory, hypotensive, antibacterial, antifungal, analgesic, anti-inflammatory and immunopotentiating. This review article is an update on the previous article published on Nigella sativa L. in this journal in 1999. It covers the medicinal properties and chemical syntheses of the alkaloids isolated from the seeds of the herb.
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Nigella sativa/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Semillas/química , Analgésicos/química , Analgésicos/aislamiento & purificación , Animales , Antiulcerosos/química , Antiulcerosos/aislamiento & purificación , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , HumanosAsunto(s)
Benzamidas/administración & dosificación , Enoxaparina/administración & dosificación , Infarto del Miocardio , Piridinas/administración & dosificación , Femenino , Humanos , Masculino , Infarto del Miocardio/complicaciones , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/mortalidad , Factores de Riesgo , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidadRESUMEN
OBJECTIVES: Indonesia faces critical challenges pertaining to human resources for health (HRH). These relate to HRH policy, planning, mismatch between production and demand, quality, renumeration, and mal-distribution. This paper provides a state of the art review of the existing conditions in Indonesia, innovations to tackle the problems, results of the innovations to date, and a picture of the on-going challenges that have yet to be met. STUDY DESIGN/METHODS: Reversing this crisis level shortage of HRH requires an inclusive approach to address the underlying challenges. In 2010 the government initiated multi-stakeholder coordination for HRH, using the Country Coordination and Facilitation approach. The process requires committed engagement and coordination of relevant stakeholders to address priority health needs. This manuscript is a formative evaluation of the program using documentary study and analysis. RESULTS: Consistent with Indonesia's decentralized health system, since 2011 local governments also started establishing provincial multi-stakeholder committees and working groups for HRH development. Through this multi-stakeholder approach with high level government support and leadership, Indonesia was able to carry out HRH planning by engaging 164 stakeholders. Multi-stakeholder coordination has produced positive results in Indonesia by bringing about a number of innovations in HRH development to achieve UHC, fostered partnerships, attracted international attention, and galvanized multi-stakeholder support in improving the HRH situation. This approach also has facilitated mobilizing technical and financial support from domestic and international partners for HRH development. CONCLUSIONS: Applying the multi-stakeholder engagement and coordination process in Indonesia has proved instrumental in advancing the country's work to achieve Universal Health Coverage and the Millennium Development Goals by 2015. Indonesia continues to face an HRH crisis but the collaborative process provides an opportunity to achieve results. Indonesia's experience indicates that irrespective of geographical or economic status, countries can benefit from multi-stakeholder coordination and engagement to increase access to health workers, strengthen health systems, as well as achieve and sustain UHC.
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Conducta Cooperativa , Fuerza Laboral en Salud/organización & administración , Humanos , Indonesia , Innovación OrganizacionalRESUMEN
There is a growing body of evidence that plant polyphenols such as resveratrol, anthocyanins, catechins, and terpenes like taxol are effectively used in the treatment of chronic conditions including cancer, Alzheimer, Parkinsonism, diabetes, aging, etc. The link between oxidative stress and inflammation is well accepted. Thus, the mechanism of action of these natural products is partly believed to be through their significant antioxidant properties. The main constituent of green tea, with clinical significance, is epigallocatechin gallate (EGCG). It has been associated with antitumor, anti-Alzheimer, and anti-aging properties, improve redox status at the tissue level possibly preventing system level structural damage. This review focuses on EGCG and its potential therapeutic role in health and disease.
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Antioxidantes/farmacología , Polifenoles/farmacología , Té/química , Animales , Antioxidantes/aislamiento & purificación , Catequina/análogos & derivados , Catequina/inmunología , Catequina/aislamiento & purificación , Humanos , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Polifenoles/aislamiento & purificaciónRESUMEN
Polydactyly, a common hereditary condition with additional digits in hands and/or feet, is a very attractive model to appreciate clinical and genetic heterogeneity. In order to get an insight into its phenotypic manifestations, we ascertained a cohort of 313 independent families with polydactyly from Pakistan; 35% cases turned out to be familial while 65% were sporadic. In majority of the index cases, polydactyly was presented as an isolated digit defect. Preaxial polydactyly types were 48.24% and postaxial were 51.8%. Familial polydactylies mainly had bilateral and symmetrical presentations, whereas sporadic cases were mostly unilateral and less often symmetrical. In the 313 index subjects a total of 508 limbs with additional digits were recorded. Variable expression was evident as the involvement of upper limbs was more common than the lower, right hand than the left, and left foot than the right. The present cohort establishes interesting epidemiological attributes of polydactyly in the Pakistani population and highlights its extraordinary clinical heterogeneity. Molecular analyses of this cohort are anticipated to elucidate novel genetic factors involved in the origin of additional digits in the growing limb and may provide clues to the role of stochastic factors in the etiology of phenotypic variability in polydactyly.
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Deformidades Congénitas del Pie/genética , Deformidades Congénitas de la Mano/genética , Polidactilia/genética , Pueblo Asiatico , Femenino , Deformidades Congénitas del Pie/fisiopatología , Deformidades Congénitas de la Mano/fisiopatología , Humanos , Masculino , Pakistán , Linaje , Polidactilia/fisiopatologíaRESUMEN
OBJECTIVE: Malvidin is a natural, biologically active polyphenol found in several fruits. It exhibits several therapeutic benefits; however, limited studies are available on its effects on neurodegenerative clinical conditions, including Parkinson's disease. The study aimed to investigate the therapeutic properties of malvidin on rotenone-triggered Parkinson's disease in an animal model. MATERIALS AND METHODS: To determine the effects of malvidin, rotenone (1.5 mg/kg) was injected subcutaneously into Wistar rats for 21 days, followed by a dose of malvidin (200 and 100 mg/kg). Behavioral tests were performed on the experimental animals before sacrifice. On the 22nd day of the experiment, biochemical tests were performed, including superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and catalase (CAT). The activity of neurotransmitters and their metabolites, including acetylcholine (ACh), acetylcholinesterase (AChE), dopamine (DA), norepinephrine (NE), serotonin (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) along with neuroinflammatory markers including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor- α (TNF-α), and nuclear factor erythroid 2-related factor 2 (Nrf-2) were estimated. Moreover, the level of the apoptotic marker, caspase-3, was also estimated. In addition, molecular docking was performed. RESULTS: The administration of rotenone resulted in oxidative stress, cholinergic imbalances, dopaminergic alternations, and increased expression of inflammatory compounds. The docking analysis revealed that malvidin displayed a favorable binding affinity for AChE, showcasing a binding energy of -9.329 Kcal/mol. CONCLUSIONS: The investigation concludes that malvidin exhibits neuroprotective effects due to its curative effects against inflammation and oxidative stress. These findings suggest that malvidin possesses therapeutic potential against rotenone-triggered behavioral, oxidative, and inflammatory abnormalities in rodents.
Asunto(s)
Caspasa 3 , Simulación del Acoplamiento Molecular , Factor 2 Relacionado con NF-E2 , Rotenona , Factor de Necrosis Tumoral alfa , Animales , Masculino , Ratas , Conducta Animal/efectos de los fármacos , Caspasa 3/metabolismo , Modelos Animales de Enfermedad , Fármacos Neuroprotectores/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: Recent research suggests that butin may also exert neuroprotective effects. However, its influence on cognitive performance and, specifically, its potential to mitigate scopolamine-induced memory impairment remains unexplored. The aim of the study is to investigate the effects of butin on the cognitive and behavioral performance of rats with scopolamine-induced memory impairment. MATERIALS AND METHODS: Scopolamine-injected memory-impediment model in rats was used to determine the efficacy of butin in higher and lower doses (10 and 20 mg/kg) for 14 days. Y-maze, along with Morris water, was used to assess the ability to recall spatial and working information. Biochemistry-related functions such as acetylcholinesterase, choline acetyltransferase, superoxide dismutase, glutathione transferase, malonaldehyde, catalase, nitric oxide, and neurotransmitters levels were estimated as indicators of free radical damage. Furthermore, we evaluated neuro-inflammatory responses by assessing tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF) and caspase-3 immuno-reactive proteins. RESULTS: When assessed through behavioral paradigms, the butin-treated group enhanced the spatial and working memory of rodents. Scopolamine caused a substantial alteration in biochemical-related parameters, neuronal enzymatic, inflammation responses and apoptosis markers prominently restored by butin. CONCLUSIONS: This study concludes that butin protects scopolamine-injected rats from behavioral impairments and neuronal damage by reducing apoptosis and neuroinflammation.