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AIM: The present systematic review with meta-analysis aimed to investigate the global association between smokeless tobacco (SLT) use and periodontitis, considering significant effect size variation based on the income levels of countries. METHODS: We searched seven databases to identify studies that assessed the prevalence of periodontitis in adult SLT users compared to non-users. The quality of studies was evaluated using the 10-item risk-of-bias tool, and publication bias was addressed through the trim-and-fill method. Sensitivity analysis utilized the leave-one-out approach. Meta-analysis and meta-regression, stratified by country income, SLT type, and smoking status, employed robust variance estimation. RESULTS: From an initial pool of 484 studies, 29 studies met the selection criteria and were subjected to qualitative synthesis. Subsequently, data from 19 studies were included in the meta-analysis. SLT users exhibited a nearly threefold greater likelihood of periodontitis compared to non-users (OR = 2.99; 95% CI: 2.10, 4.27; p < .01). The pooled estimate did not vary significantly based on the type of SLT used or concurrent smoking. However, the odds of periodontitis varied according to the economic level of the country; the pooled estimate was higher in high-income countries (OR = 1.69; 95% CI: 1.20, 2.37; p < .01) and even higher in lower-middle-income and lower-income countries (OR = 3.91; 95% CI: 2.66, 5.77; p < .01). CONCLUSIONS: Smokeless tobacco users have a higher likelihood of developing periodontitis. This study underscores global disparities in the SLT-periodontitis relationship, highlighting the need for targeted interventions, particularly in economically challenged areas where SLT use is largely unregulated.
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Since Alzheimer disease is one of the most prevalent types of dementia with a high mortality and disability rate, so development of multi-target drugs becomes the major strategy for battling AD. This study shows the development of a series of quinazolinone based derivatives as novel, multifunctional anti-AD drugs that exhibit both cholinesterase inhibitoryand anti-inflammatory properties. The preliminary results of the in vitro AChE inhibition activity showed that compounds 4b, 5a, 6f, 6h and 7b were better represented for further evaluation. Furthermore, in-vivo AChE inhibition activity and behavior Morris water maze test against donepezil as reference drug were evaluated. Additionally, hippocampal inflammatory markers; TNF-α, NFĸB, IL-1ß and IL-6 and antioxidant markers; SOD and MDA were assessed to evaluate the efficacy of quinazolinone derivatives against AD hallmarks. The results showed that 6f, 6h and 7b have promising anti-acetylcholinesterase, anti-inflammatory and antioxidant activities thus, have a significant effect in treatment of AD. Moreover, Histopathological examination revealed that 6f, 6h and 7b derivatives have neuroprotective effect against neuronal damage caused by induced scopolamine model in mice. Finally, the binding ability of the synthesized derivatives to the target, AChE was investigated through molecular docking which reflected significant interactions to the target based on their docking binding scores. Hence, the newly designed quinazolinone derivatives possess promising anti-acetylcholinesterase activity and challenging for the management of AD in the future.
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Enfermedad de Alzheimer , Fármacos Neuroprotectores , Ratones , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Simulación del Acoplamiento Molecular , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/química , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/uso terapéutico , Inhibidores de la Colinesterasa/química , Antiinflamatorios/farmacología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/química , Diseño de Fármacos , Relación Estructura-Actividad , Péptidos beta-Amiloides/metabolismoRESUMEN
It has been proven that stress, mainly in the early years of life, can lead to anxiety and mood problems. Current treatments for psychiatric disorders are not enough, and some of them show intolerable side effects, emphasizing the urgent need for new treatment targets. Hence, a better understanding of the different brain networks, which are involved in the response to anxiety and depression, may evoke treatments with more specific targets. One of these targets is ß-catenin that regulates brain circuits. ß-Catenin has a dual response toward stress, which may influence coping or vulnerability to stress response. Indeed, ß-catenin signaling involves several processes such as inflammation-directed brain repair, inflammation-induced brain damage, and neurogenesis. Interestingly, ß-catenin reduction is accompanied by low neurogenesis, which leads to anxiety and depression. However, in another state, this reduction activates a compensatory mechanism that enhances neurogenesis to protect against depression but may precipitate anxiety. Thus, understanding the molecular mechanism of ß-catenin could enhance our knowledge about anxiety and depression's pathophysiology, potentially improving clinical results by targeting it. Herein, the different states of ß-catenin were discussed, shedding light on possible drugs that showed action on psychiatric disorders through ß-catenin.
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Depresión , beta Catenina , Humanos , Ansiedad/tratamiento farmacológico , Depresión/tratamiento farmacológico , Inflamación , NeurogénesisRESUMEN
In dengue-endemic regions, the co-infection with SARS-CoV-2 and dengue is a significant health concern. Therefore, we performed a literature search for relevant papers in seven databases on 26 Spetember 2021. Out of 24 articles, the mortality rate and intensive care unit (ICU) admission were 19.1% and 7.8%, respectively. The mean hospital stay was 11.4 days. In addition, we identified two pregnancies with dengue and COVID-19 co-infection; one ended with premature rupture of membrane and intrauterine growth restriction fetus, while the other one ended with maternal mortality and intrauterine fetal death. COVID-19 and dengue co-infection had worse outcomes regarding mortality rates, ICU admission, and prolonged hospital stay. Thus, wise-decision management approaches should be adequately offered to these patients to enhance their outcomes. Establishing an early diagnosis might be the answer to reducing the estimated significant burden of these conditions.
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COVID-19 , Coinfección , Dengue , Nacimiento Prematuro , Coinfección/epidemiología , Dengue/complicaciones , Dengue/diagnóstico , Dengue/epidemiología , Femenino , Humanos , Embarazo , SARS-CoV-2RESUMEN
Azithromycin (AZM) is commonly used in Covid-19 patients based on low-quality evidence, increasing the risk of developing adverse events and antimicrobial resistance. The current systematic review and meta-analysis investigated the safety and efficacy of AZM in treating Covid-19 patients using published randomized controlled trials. Google Scholar, PubMed, Scopus, Cochrane Library, Clinical Trials.gov, MEDLINE, bioRxiv and medRxiv were searched for relevant studies. The random-effects model was used to pool estimates using the Paule-Mandel estimate for heterogeneity. The odds ratio and raw difference in medians were used for dichotomous and continuous outcomes, respectively. The analysis included seven studies with 8822 patients (median age, 55.8 years; 61% males). The risk of bias was assessed as 'low' for five of the seven mortality results and as 'some concerns' and 'high' in one trial each. There were 657/3100 (21.2%) and 1244/5654 (22%) deaths among patients randomized to AZM and standard of care, respectively. The use of AZM was not associated with mortality in Covid-19 patients (OR = 0.96, 95% CI 0.88-1.05, p = 0.317 based on the random-effect meta-analysis). The use of AZM was not associated with need for invasive mechanical ventilation (OR = 0.96, 95% CI 0.49-1.87, p = 0.85) and length of stay (Δ = 1.11, 95% CI -2.08 to 4.31, p = 0.49). The results show that using AZM as routine therapy in Covid-19 patients is not justified due to lack of efficacy and potential risk of bacterial resistance that is not met by an increased clinical benefit.
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Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Antibacterianos/efectos adversos , Azitromicina/efectos adversos , COVID-19/diagnóstico , Humanos , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , SARS-CoV-2RESUMEN
Parkinson's disease (PD) patients who contracted Coronavirus disease 2019 (Covid-19) had a decline in motor functions; nevertheless, there is limited evidence on whether PD patients have a higher risk for contracting Covid-19 or have worse outcomes. This is the first systematic review and meta-analysis to review the impact of PD on the prognosis of Covid-19 patients. We performed a systematic search through seven electronic databases under the recommendations of the Preferred Reporting Items for Systematic Review and Meta-analyses statement (PRISMA) guidelines. The R software version 4.0.2 was used to calculate pooled sample sizes and their associated confidence intervals (95%CI). Finally, we included 13 papers in this study. The pooled prevalence rate of Covid-19 was 2.12% (95%CI: 0.75-5.98). Fever, cough, fatigue and anorexia were the most common symptoms with a rate of 72.72% (95% CI: 57.3 - 92.29), 66.99% (95% CI: 49.08-91.42), 61.58% (95% CI: 46.69-81.21) and 52.55% (95% CI: 35.09-78.68), respectively. The pooled rates were 39.89% (95% CI: 27.09-58.73) for hospitalisation, 4.7% (95% CI: 1.56-14.16) for ICU admission and 25.1% (95%CI: 16.37-38.49) for mortality. On further comparison of hospitalisation and mortality rates among Covid-19 patients with and without PD, there were no significant differences. In conclusion, the prevalence and prognosis of Covid-19 patients seem comparable in patients with PD and those without it. The increased hospitalisation and mortality may be attributed to old age and co-morbidities.
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COVID-19 , Enfermedad de Parkinson , COVID-19/epidemiología , Hospitalización , Humanos , Enfermedad de Parkinson/epidemiología , Prevalencia , SARS-CoV-2RESUMEN
BACKGROUND: To compare the efficacy and safety of standard percutaneous nephrolithotomy (PCNL) with mini- PCNL for kidney stones 2-4 cm. METHODS: Eighty patients were enrolled in a comparative study, they were randomly divided into mini-PCNL group (n = 40) and standard-PCNL (n = 40). Demographic characteristics, perioperative events, complications, stone free rate (SFR) were reported. RESULTS: Both groups showed no significant difference in clinical data about age, stone location, back pressure changes, and body mass index. The mean operative time was (95 ± 17.9 min) in mini-PCNL, and (72.1 ± 14.9 min). Stone free rate were 80% and 85% in mini-PCNL and standard-PCNL respectively. Intra-operative complications, post-operative need for analgesia, hospital stay were significantly higher in standard-PCNL compared to mini-PCNL (85% vs. 80%). The study followed CONSORT 2010 guidelines for reporting parallel group randomization. CONCLUSION: Mini-PCNL is an effective and safe treatment of kidney stones 2-4 cm, it has the advantage over standard-PCNL being has less intra-operative events, less post-operative analgesia, shorter hospital stay, while operative time and stone free rate are comparable when considering multiplicity, hardness, and site of stones.
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Cálculos Renales , Litotricia , Nefrolitotomía Percutánea , Nefrostomía Percutánea , Humanos , Cálculos Renales/cirugía , Resultado del Tratamiento , Nefrolitotomía Percutánea/métodos , Tiempo de Internación , Nefrostomía Percutánea/métodosRESUMEN
The aim was to enhance the dissolution rate and in vivo efficacy of flubendazole against trichinella spiralis. Flubendazole nanocrystals were developed by controlled anti-solvent recrystallization. Saturated flubendazole solution was prepared in DMSO. This was injected into phosphate buffer (pH 7.4) containing Aerosil 200, Poloxamer 407 or sodium lauryl sulphate (SLS) while mixing using paddle mixer. The developed crystals were separated from DMSO/aqueous system by centrifugation. The crystals were characterized using DSC, X-ray diffraction and electron microscopy. The crystals were suspended in Poloxamer 407 solution and dissolution rate was monitored. Optimal formulation was administered to Trichinella spiralis infected mice. Administration protocol attacked the parasite in intestinal, migrating and encysted phases. The crystals were spherical nanosized with formulation employing 0.2% Poloxamer 407 as stabilizer being optimum with size of 743.1 nm. DSC and X-ray supported particle size reduction with partial amorphization. Optimal formulation showed fast dissolution to deliver 83.1% after 5 min. Nanocrystals provided complete eradication of intestinal Trichinella and reduced larval count by 90.27 and 85.76% in migrating and encysted phases compared with marginal effect in case of unprocessed flubendazole. The efficacy was clearer from improved histopathological features of the muscles. The study introduced nano-crystallization for enhanced dissolution and in vivo efficacy of flubendazole.
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Trichinella spiralis , Ratones , Animales , Solubilidad , Poloxámero , DimetilsulfóxidoRESUMEN
OBJECTIVE: To compare the efficacy and morbidity of transurethral cystolithotripsy (TUCL) and percutaneous CL (PCCL) in the management of bladder stones in male children. PATIENTS AND METHODS: A total of 100 boys, aged <14 years with a single bladder or urethral stone of <30 mm, were randomised into two equal groups. Initial diagnostic urethro-cystoscopy and push back of urethral stones were done for patients in both groups. Patients in Group A had TUCL, while those in Group B had PCCL through a 20-F sheath using a 12-F nephroscope. The two groups were compared regarding preoperative criteria, intraoperative details, and postoperative outcomes. RESULTS: The patients in this study had a median (range) age of 36 (4-144) months and stone size of 10 (5-26) mm. There was no statistically significant difference between the two groups for preoperative criteria. The assigned procedure was successful in 48 (96%) patients in Group A and 49 (98%) in Group B (P = 1). Complications were encountered in 11 (22%) patients in Group A and five (10%) in Group B (P = 0.171). The median (range) operative time was 21.5 (4-90) min in Group A and 13 (5-70) min in Group B (P < 0.001). In all, 47 (94%) stones needed disintegration in Group A vs 22 (44%) in Group B (P < 0.001). CONCLUSION: Both techniques have comparable success and complications rates. However, PCCL has a shorter operative time and less need for stone disintegration.
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Litotricia , Cálculos de la Vejiga Urinaria , Niño , Cistoscopía/métodos , Humanos , Litotricia/métodos , Masculino , Tempo Operativo , Uretra , Cálculos de la Vejiga Urinaria/cirugíaRESUMEN
BACKGROUND: Early detection of metastasis and recurrence of Ewing sarcoma (ES) is important for early management. This work aimed to detect CD99+ , CD45- cells in peripheral blood by flow cytometry (FC) before and during chemotherapy and evaluate their prognostic significance. PROCEDURE: This prospective cohort study was carried out on 60 children newly diagnosed with ES at Children Cancer Hospital-Egypt 57357 and 40 healthy children control group. Detection of CD99+ , CD45- cells in peripheral blood was accomplished by FC at baseline before treatment and after five cycles of chemotherapy. Samples were classified as positive if they had more than the upper limit of cells observed in the control cases. Correlation between FC results and relapse and overall survival (OS) after one year was performed. RESULTS: Median percentage of CD99+ , CD45- cells was significantly increased in patients compared with controls (0.002% vs 0%, respectively, P < 0.001). Post-cycle 5 CD99+ , CD45- cells were increased in 12 patients, of them 11 patients' disease had either relapsed or progressed. Post-cycle 5 CD99+ ; CD45- cells had a 73.3% sensitivity and 97.8% specificity for predicting relapse or progression, whereas baseline only had 6.7% sensitivity and 77.8% specificity. The hazard ratio for mortality in the post-cycle 5 positive group was 18.4 [95% confidence interval (1.86 to 181.46)] times that of the negative group. One year OS was 91.67%. CONCLUSION: Post-cycle 5 CD99+ , CD45- cells in peripheral blood by FC is a strong predictor for relapse, progression, and mortality whereas baseline is a poor predictor in newly diagnosed patients with ES.
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Antígeno 12E7 , Neoplasias Óseas , Antígenos Comunes de Leucocito , Tumores Neuroectodérmicos Periféricos Primitivos , Sarcoma de Ewing , Antígeno 12E7/sangre , Neoplasias Óseas/sangre , Neoplasias Óseas/diagnóstico , Niño , Citometría de Flujo , Humanos , Antígenos Comunes de Leucocito/sangre , Recurrencia Local de Neoplasia , Pronóstico , Estudios Prospectivos , Sarcoma de Ewing/sangre , Sarcoma de Ewing/diagnósticoRESUMEN
BACKGROUND: Coagulopathy and thromboembolic events are common in Covid-19 patients and are poor prognostic factors. Controversy exists regarding the potential of anticoagulation (AC) to reduce mortality and incidence of thromboembolic events in Covid-19 patients. The current systematic review and meta-analysis investigated the association between anticoagulants and mortality in adult hospitalized COVID-19 patients using the available published non-randomized studies. METHODS: Google Scholar, PubMed, Scopus, the Cochrane Library and Clinical Trials.gov were searched for relevant studies. A meta-analysis of adjusted and unadjusted estimates was performed. The relative risk was used as a measure of effect. The random-effects model was used to pool estimates using the generic inverse variance method. RESULTS: Sixteen studies were included in the quantitative data synthesis. Results showed a statistically significant association between AC and mortality (RR = 0.56, 95% CI 0.36; 0.92, p = 0.02). Both therapeutic (Relative risk [RR] = 0.4, 95% CI 0.27; 0.57) and prophylactic AC (RR = 0.54, 95% CI 0.41; 0.71) were associated with lower risk of mortality. Pre-admission AC was not associated with mortality (RR = 0.84, 95% CI 0.49; 1.43, p > 0.05) while prophylactic AC was associated with higher risk of mortality compared to therapeutic AC (RR = 1.58, 95% CI 1.34; 1.87, p < 0.001). CONCLUSION: Findings support the association of AC with mortality in Covid-19 patients. The results, synthesized from mostly low-quality studies, show that prophylactic and therapeutic AC might reduce mortality in Covid-19 patients. Findings suggest that therapeutic doses might be associated with better survival compared to prophylactic doses.
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Anticoagulantes/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Coagulación Intravascular Diseminada/tratamiento farmacológico , Embolia Pulmonar/tratamiento farmacológico , SARS-CoV-2/patogenicidad , COVID-19/sangre , COVID-19/mortalidad , COVID-19/patología , Estudios de Casos y Controles , Estudios de Cohortes , Coagulación Intravascular Diseminada/sangre , Coagulación Intravascular Diseminada/mortalidad , Coagulación Intravascular Diseminada/patología , Esquema de Medicación , Hospitalización , Humanos , Oportunidad Relativa , Profilaxis Pre-Exposición/métodos , Embolia Pulmonar/sangre , Embolia Pulmonar/mortalidad , Embolia Pulmonar/patología , Riesgo , SARS-CoV-2/metabolismo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Left ventricular hypertrophy is a common finding in patients with ischemic heart disease and is associated with mortality in patients with cardiovascular disease (CVD). Metformin, an antidiabetic drug, has been shown to reduce oxidative stress and left ventricular mass index (LVMI) in animal hypertrophy models. We summarized evidence regarding the effect of metformin on LVMI and LVEF. METHODS: Electronic databases were searched for randomized clinical trials (RCTs) that used metformin in non-diabetic patients with or without pre-existing CVD. The standardized mean change using change score standardization (SMCC) was calculated for each study. The random-effects model was used to pool the SMCC across studies. Meta-regression analysis was used to assess the association of heart failure (HF), metformin dose, and duration with the SMCC. RESULTS: Data synthesis from nine RCTs (754 patients) showed that metformin use resulted in higher reduction in LVMI after 12 months (SMCC = -0.63, 95% CI - 1.23; - 0.04, p = 0.04) and an overall higher reduction in LVMI (SMCC = -0.5, 95% CI - 0.84; - 0.16, p < 0.01). These values equate to absolute values of 11.3 (95% CI 22.1-0.72) and 8.97 (95% CI 15.06-2.87) g/m2, respectively. The overall improvement in LVEF was also higher in metformin users after excluding one outlier (SMCC = 0.26, 95% CI 0.03-0.49, P = 0.03) which translates to a higher absolute improvement of 2.99% (95% CI 0.34; 5.63). Subgroup analysis revealed a favorable effect for metformin on LVEF in patients who received > 1000 mg/day (SMCC = 0.28, 95% CI 0.04; 0.52, P = 0.04), and patients with HF (SMCC = 0.23; 95% CI 0.1; 0.36; P = 0.004). These values translate to a higher increase of 2.64% and 3.21%, respectively. CONCLUSION: Results suggest a favorable effect for metformin on LVMI and LVEF in patients with or without pre-existing CVD. Additional trials are needed to address the long-term effect of metformin. Registration The study was registered on the PROSPERO database with the registration number CRD42021239368 ( https://www.crd.york.ac.uk/prospero ).
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Enfermedades Cardiovasculares , Insuficiencia Cardíaca , Metformina , Enfermedades Cardiovasculares/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Hipertrofia Ventricular Izquierda/inducido químicamente , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Tobacco consumption remains a public health issue and is one of the major causes of death in India. This study presents a validated conceptual model to assess the interaction between education, perceived application of tobacco control measures, type of tobacco and their effects on the intention to quit tobacco. Additionally, the direct and mediating roles of tobacco use -frequency, -duration, and -dependency on the intention to quit is also investigated. METHODS: An analytical cross-sectional study was carried out, and data from tobacco users of six randomly selected states in India was collected via face-to-face interviews. Structural equation modeling (SEM) was performed using R v 3.6.3 to test the model fit and to explore the association between tobacco control measures and the intention to quit tobacco. RESULTS: From 1962 tobacco users, 43.7% wanted to quit tobacco immediately. Tambakoo (57.7%) was the most common type of tobacco used and 68.9% said that minors could buy tobacco. Findings from SEM showed that that one standard deviation (SD) increase in the perceived application of tobacco control measures is directly associated with a 0.181 SD increase in the intention to quit tobacco (B = 0.181, P < 0.001), and this effect was partially mediated by frequency of tobacco consumption (B = 0.06, P < 0.05). Also, a better education level was associated with a higher intention to quit tobacco (B = 0.14, P < 0.001). CONCLUSIONS: To conclude, the application of tobacco control measures and a better education level may positively affect the intention to quit tobacco. The frequency of tobacco use and the number of influencers play an essential role in deciding to quit. In future, longitudinal studies are recommended to further substantiate the evidence.
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Intención , Cese del Hábito de Fumar , Estudios Transversales , Humanos , Análisis de Clases Latentes , Nicotiana , Uso de Tabaco/prevención & controlRESUMEN
PURPOSE: Primary malignant bone tumors of the hand are rare in children. Resection and reconstruction of the digit are challenging and have been described in case reports. This retrospective study describes the functional and oncologic outcomes of resection and reconstruction using a nonvascularized fibular bone graft in a cohort of children. METHODS: A total of 5 children were included. The mean age at diagnosis was 7.6 years (range, 1.6-12 years). Histologic diagnosis showed Ewing sarcoma in 3 and osteosarcoma in 2 patients. Four tumors were located in the metacarpal bones of the fingers, and 1 was located in the thumb. Four patients were treated with chemotherapy. All the patients were treated with wide resection and a cement spacer. This was followed by second stage reconstruction using a nonvascularized fibular bone graft. In tumors of the fingers, carpometacarpal joint fusion with a neighboring carpal bone was performed, whereas a pseudoarthrosis was created between the graft and the base of the proximal phalanx. In the thumb's case, the opposite was done, with fusion at the metacarpophalangeal joint and a pseudoarthrosis at the carpometacarpal joint. RESULTS: The mean follow-up duration was 5.5 years (range, 2-9 years). Surgical margins were negative in all the patients. At their latest follow-up visit, none of the patients developed systemic or local recurrence. Two complications required a revision surgery, one due to graft subluxation and the other due to nonunion. At their final follow-up examination, the mean total arc of movement was 80° (range, 60°-100°), and all the patients were able to resume their grasping and writing capabilities. CONCLUSIONS: The resection and reconstruction of primary malignant bone tumors of the metacarpals using a nonvascularized fibular bone graft in children can preserve the cosmesis and function of the digit without jeopardizing oncologic outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.
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Neoplasias Óseas , Osteosarcoma , Procedimientos de Cirugía Plástica , Seudoartrosis , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Trasplante Óseo , Niño , Preescolar , Peroné/cirugía , Peroné/trasplante , Humanos , Lactante , Osteosarcoma/patología , Osteosarcoma/cirugía , Seudoartrosis/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Autophagy and mitochondrial deficits are characteristics of early phase of Alzheimer's disease (AD). Sodium-glucose cotransporter-2 inhibitors have been nominated as a promising class against AD hallmarks. However, there are no available data yet to discuss the impact of gliflozins on autophagic pathways in AD. Peripherally, dapagliflozin's (DAPA) effect is mostly owed to autophagic signals. Thus, the goal of this study is to screen the power of DAPA centrally on LKB1/AMPK/SIRT1/mTOR signaling in the ovariectomized/D-galactose (OVX/D-Gal) rat model. Animals were arbitrarily distributed between 5 groups; the first group undergone sham operation, while remaining groups undergone OVX followed by D-Gal (150 mg/kg/day; i.p.) for 70 days. After 6 weeks, the third, fourth, and fifth groups received DAPA (1 mg/kg/day; p.o.); concomitantly with the AMPK inhibitor dorsomorphin (DORSO, 25 µg/rat, i.v.) in the fourth group and the SIRT1 inhibitor EX-527 (10 µg/rat, i.v.) in the fifth group. DAPA mitigated cognitive deficits of OVX/D-Gal rats, as mirrored in neurobehavioral task with hippocampal histopathological examination and immunohistochemical aggregates of p-Tau. The neuroprotective effect of DAPA was manifested by elevation of energy sensors; AMP/ATP ratio and LKB1/AMPK protein expressions along with autophagic markers; SIRT1, Beclin1, and LC3B expressions. Downstream the latter, DAPA boosted mTOR and mitochondrial function; TFAM, in contrary lessened BACE1. Herein, DORSO or EX-527 co-administration prohibited DAPA's actions where DORSO elucidated DAPA's direct effect on LKB1 while EX-527 mirrored its indirect effect on SIRT1. Therefore, DAPA implied its anti-AD effect, at least in part, via boosting hippocampal LKB1/AMPK/SIRT1/mTOR signaling in OVX/D-Gal rat model.
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Enfermedad de Alzheimer , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Animales , Ratas , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/patología , Proteínas Quinasas Activadas por AMP/metabolismo , Secretasas de la Proteína Precursora del Amiloide/farmacología , Ácido Aspártico Endopeptidasas/farmacología , Autofagia , Galactosa/farmacología , Sirtuina 1/metabolismo , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Serina-Treonina Quinasas TORRESUMEN
This randomised controlled trial aimed to compare the effect of early and delayed pushing during the second stage of labour in women with occipitoposterior (OP) malposition. It included 184 nulliparous women with OP position randomised to early pushing in which women were allowed to push within one hour after full cervical dilatation or delayed pushing in which women were asked not to push for maximum of three hours or start pushing when the vertex was visible. The primary outcome was successful vaginal delivery. The rate of spontaneous vaginal delivery was significantly higher in the early pushing group (80.4 vs. 60.9%, p=.004) while the rate of instrumental vaginal delivery (30.4 vs. 15.4%) and CS (8.7 vs. 4.3%) was significantly higher in the delayed pushing group. Women in the delayed pushing group showed a significantly longer duration of the second stage (129.4 ± 7.5 vs. 61.6 ± 15.3 minutes, p<.001) and shorter duration of pushing (219.8 ± 74.8 vs. 693.9 ± 145.2 seconds, p<.001) .The rate of 2nd and 3rd degree perineal lacerations (19.6 and 13% vs. 5.4 and 8.7% respectively, p=.013) and vaginal tears (41.3 vs. 8.7%, p<.001) was significantly higher in the early pushing group. We concluded that early pushing during the second stage of labour is associated with higher rates of spontaneous vaginal delivery and vaginal and perineal lacerations.Clinical trial registration NCT03121274.Impact StatementWhat is already known on this subject? Occipitoposterior malposition is common during delivery especially in primigravida and is associated with higher rates of instrumental delivery and caesarean section. It can be managed through early or delayed pushing.What the results of this study add? Early pushing is associated with higher rates of spontaneous vaginal delivery, perineal and vaginal tears, shorter duration of second stage of labour, shorter duration of pushing, lower rates of both instrumental vaginal delivery and caesarean section.What the implications are of these findings for clinical practice and/or further research? Early pushing during the second stage of labour is associated with higher rates of spontaneous vaginal delivery and vaginal and perineal lacerations in women with OP malposition and should be tried and not delaying the pushing.
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Anestesia Epidural , Parto Obstétrico/estadística & datos numéricos , Presentación en Trabajo de Parto , Segundo Periodo del Trabajo de Parto/fisiología , Complicaciones del Trabajo de Parto/fisiopatología , Adulto , Parto Obstétrico/métodos , Femenino , Número de Embarazos , Humanos , Primer Periodo del Trabajo de Parto , Laceraciones/etiología , Complicaciones del Trabajo de Parto/etiología , Perineo/lesiones , Embarazo , Factores de TiempoRESUMEN
BACKGROUND: Breastfeeding is beneficial to both mother and infant. However, overlap of lactation with pregnancy and short recuperative intervals may impact mothers nutritionally. We aimed to investigate the possible effects of pregnancy during breastfeeding. METHODS: In October 2018, we searched systematically in nine electronic databases to investigate any association of breastfeeding during pregnancy with fetal and/or maternal outcomes. The study protocol was registered in PROSPERO (CRD41017056490). A meta-analysis was done to detect maternal and fetal outcomes and complications during pregnancy. Quality assessment was performed using the Australian Cancer Council bias tool for included studies. RESULTS: With 1992 studies initially identified, eight were eligible for qualitative analysis and 12 for quantitative analysis. Our results showed no significant difference in different abortion subtypes between lactating and non-lactating ones. In delivery, no difference between two groups regarding the time of delivery in full-term healthy, preterm delivery and preterm labor. No significant difference was detected in rates of antepartum, postpartum hemorrhage and prolonged labor between two groups. The women with short reproductive intervals may have higher supplemental intake and greater reduction fat store. The present studies showed that breastfeeding during pregnancy does not lead to adverse outcomes in the mother and her fetus in normal low-risk pregnancy, although it may lead to the nutritional burden on the mother. CONCLUSION: The present studies showed that breastfeeding during pregnancy did not lead to the adverse outcomes in the mother and her fetus.
Asunto(s)
Lactancia Materna , Complicaciones del Trabajo de Parto , Australia/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Lactancia , Periodo Posparto , EmbarazoRESUMEN
BACKGROUND: The rate of multiple pregnancies in IVF/ICSI ranges from 20 to 30%. The incidence of preterm birth in multiple pregnancies is as high as 60% and is even higher in pregnancies conceived after IVF & ICSI. The effect of progesterone on prevention of preterm birth in twins is controversial. Our group has proven a positive effect in reduction of preterm birth, by starting progesterone from the mid-trimester, in exclusively IVF/ICSI singleton pregnancies but not twins. The purpose of our current study was to explore the effect of earlier administration of natural progesterone, in IVF/ICSI twin pregnancies starting at 11-14 weeks for prevention of preterm birth. METHODS: This is a double-blind, placebo controlled, single center, randomized clinical trial. Women with dichorionic twin gestations, having an IVF/ICSI trial were randomized to receive natural rectal progesterone (800 mg daily) vs placebo, starting early from 11 to 14 weeks. They also received oral and vaginal antimicrobial agents as part of our routine treatment for vaginitis and urinary tract infection. They were randomized regardless of cervical length and had no previous history of preterm birth or known Mullerian anomalies. The primary outcome was spontaneous preterm birth rate before 37 weeks. The secondary outcome was; spontaneous preterm birth before 34, 32, 28 weeks and neonatal outcome. RESULTS: A total of 203 women were randomized to both groups, final analysis included 199 women as 4 were lost to follow up. The base line characteristics as well as gestational age at delivery were not significantly different between the study and the placebo group (34.7 ± 3.6 vs 34.5 ± 4.5, P = 0.626). Progesterone administration was not associated with a significant decrease in the spontaneous preterm birth rates before 37 weeks (73.5% vs 68%, P = 0.551), before 34 (20.6% vs 21.6%, P = 0.649), before 32 (8.8% vs 12.4%, P = 0.46) & before 28 (4.9% vs 3.1%, P = 0.555) weeks. CONCLUSIONS: Rectal natural progesterone starting from the first trimester in IVF/ICSI twin pregnancies did not reduce spontaneous preterm birth. TRIAL REGISTRATION: The trial was registered on 31 January 2014 at www.ISRCTN.com, number 69810120.
Asunto(s)
Fertilización In Vitro , Embarazo Gemelar , Nacimiento Prematuro/epidemiología , Progesterona/uso terapéutico , Progestinas/uso terapéutico , Inyecciones de Esperma Intracitoplasmáticas , Adulto , Tasa de Natalidad , Método Doble Ciego , Intervención Médica Temprana , Femenino , Edad Gestacional , Humanos , Recién Nacido , Embarazo , Resultado del Embarazo/epidemiología , Nacimiento Prematuro/prevención & control , Progesterona/administración & dosificación , Progestinas/administración & dosificaciónRESUMEN
PURPOSE: To assess the value of various grey-scale ultrasound, 2D color Doppler, and 3D power Doppler sonographic markers in predicting major intraoperative blood loss during planned cesarean hysterectomy for cases diagnosed with placenta accreta spectrum (PAS) disorders. METHODS: 50 women diagnosed with PAS were scanned the day before planned delivery and hysterectomy for various sonographic markers indicative of placental invasion. These women were then later divided according to blood loss in two groups: group A (minor hemorrhage, < 2500 ml), and group B (major hemorrhage, > 2500 ml), and the data were analyzed. RESULTS: The odds ratio (OR) for major hemorrhage was as follows for the following sonographic markers: 'number of lacunae > 4' OR 3.8 95% CI (1.0-13.8) (p = 0.047); 'subplacental hypervascularity' OR 10.8 95% CI (1.2-98.0) (p = 0.035); 'tortuous vascularity with 'chaotic branching' OR 10.8 95%CI (1.2-98.0) (p = 0.035); 'numerous coherent vessels involving the serosa-bladder interface OR 14.6 95% CI (2.7-80.5) (p = 0.002); and 'presence of bridging vessels OR 2.9 95% CI (1.4-6.9) (p = 0.005). Only the presence of numerous coherent vessels involving the bladder-serosal interface (p = 0.002) was proven to be independent predictor of major hemorrhage during hysterectomy. CONCLUSION: The use of 2D color Doppler and 3D power Doppler can help predict massive hemorrhage in cases of PAS disorders.
Asunto(s)
Pérdida de Sangre Quirúrgica , Cesárea/efectos adversos , Histerectomía/efectos adversos , Miometrio/diagnóstico por imagen , Placenta Accreta/diagnóstico por imagen , Ultrasonografía Doppler en Color/métodos , Ultrasonografía Doppler/métodos , Adulto , Femenino , Humanos , Miometrio/irrigación sanguínea , Placenta/diagnóstico por imagen , Placenta Accreta/cirugía , Embarazo , Resultado del Embarazo , Sensibilidad y EspecificidadRESUMEN
PURPOSE: When adenotonsillar hypertrophy (ATH) is encountered in children during cleft palate (CP) repair, the decision for adenotonsillectomy is challenging. The aim of this study was to evaluate the effectiveness of adenotonsillectomy done during CP repair for children with ATH on speech and breathing. METHODS: Nine children with CP and ATH underwent adenotonsillectomy prior to palatoplasty in same sitting. The age of patients ranged between 1.5 and 3.5 years with a mean age of 2.3 years at the time of operation. Auditory perceptual assessment (APA), nasometric assessment, and velopharyngeal function evaluation were performed when the children reached the age of 4 years. RESULTS: No children developed obstructive breathing episodes postoperatively as witnessed by parents. APA showed normal nasality in six patients and mild hypernasality in three patients. Nasalance scores for both nasal and oral sentences were found to be comparable with that of normal children of the same age. Velopharyngeal closure was seen competent in four patients, borderline competent in three patients, and borderline incompetent in two patients. CONCLUSION: Performing adenotonsillectomy during CP repair does not deleteriously affect the speech and it prevents the occurrence of postoperative obstructive breathing episodes that may be caused by the hypertrophied tonsils and/or adenoid.