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Parecoxib decreases cellular growth and Bcl‐2 protein levels in primary cultures of keloid fibroblasts

Abstract

Keloids seem to overexpress cyclo-oxygenase-2 (COX-2), suggesting a role in its deregulated pathway in inducing an altered epithelial-mesenchymal interaction, which may be responsible for the overgrowth of dermal components resulting in scars or keloid lesions. This study aimed to evaluate the effect of Parecoxib, a COX-2 inhibitor, on cell growth in fibroblast primary cultures obtained from human keloid tissues. Tissue explants were obtained from patients who underwent intralesional excision of untreated keloids; central fractions were isolated from keloid tissues and used for establishing distinct primary cultures. Appropriate aliquots of Parecoxib, a COX-2 inhibitor were diluted to obtain the concentration used in the experimental protocols in vitro (1, 10 or 100 μM). Treatment with Parecoxib (at all concentrations) caused a significant decrease in cellular growth from 24 hours onwards, and with a maximum at 72 hours (P < .02). Moreover, at 72 hours Parecoxib significantly reduced cellular vitality. Parecoxib treatment also induced an increase in fragmented nuclei with a maximum effect at 100 μM and a significant decrease in Bcl-2 and an increase in activated caspase-3 protein levels at 72 hours compared with control untreated cultures. Our findings suggest a potential use of the COX-2 inhibitor, Parecoxib, as the therapy for keloids.

Effect of antiplatelet therapy after COVID-19 diagnosis: A systematic review with meta-analysis and trial sequential analysis

by Hong Duo, Mengying Jin, Yanwei Yang, Rewaan Baheti, Yujia Feng, Zirui Fu, Yuyue Jiang, Lanzhuoying Zheng, Jing Wan, Huaqin Pan

Background

Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic disease in the venous and arterial circulations.

Methods

Based on the current debate on antiplatelet therapy in COVID-19 patients, we performed a systematic review and meta-analysis to investigate the effect of antiplatelet treatments. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2023, and only included Randomized clinical trials. The study followed PRISMA guidelines and used Random-effects models to estimate the pooled percentage and its 95% CI.

Results

Five unique eligible studies were included, covering 17,950 patients with COVID-19. The result showed no statistically significant difference in the relative risk of all-cause death in antiplatelet therapy versus non-antiplatelet therapy (RR 0.94, 95% CI, 0.83–1.05, P = 0.26, I2 = 32%). Compared to no antiplatelet therapy, patients who received antiplatelet therapy had a significantly increased relative risk of major bleeding (RR 1.81, 95%CI 1.09–3.00, P = 0.02, I2 = 16%). The sequential analysis suggests that more RCTs are needed to draw more accurate conclusions. This systematic review and meta-analysis revealed that the use of antiplatelet agents exhibited no significant benefit on all-cause death, and the upper bound of the confidence interval on all-cause death (RR 95% CI, 0.83–1.05) suggested that it was unlikely to be a substantiated harm risk associated with this treatment. However, evidence from all RCTs suggested a high risk of major bleeding in antiplatelet agent treatments.

Conclusion

According to the results of our sequential analysis, there is not enough evidence available to support or negate the use of antiplatelet agents in COVID-19 cases. The results of ongoing and future well-designed, large, randomized clinical trials are needed.

Early Neolithic pastoral land use at Alsónyék-Bátaszék, Hungary (Starčevo culture): New insights from stable isotope ratios

by Magdalena Blanz, Marie Balasse, Delphine Frémondeau, Erika Gál, Anett Osztás, Anna Zs. Biller, Éva Á. Nyerges, Denis Fiorillo, Eszter Bánffy, Maria Ivanova

The earliest introduction of livestock (cattle, goats, sheep, pigs) into the Carpathian Basin was an important step towards farming expansion into continental Europe. This spread beyond the environments of the southern Balkans was accompanied by a reduction in the spectrum of cultivated crops, changes in the relative representation of different domestic animals, and, most likely, adaptations of husbandry practices. How the earliest farmers in the Carpathian Basin kept their domestic stock is still understudied. We explored early animal management and land use strategies at the Starčevo settlement at Alsónyék-Bátaszék, Hungary (Early Neolithic, ca. 5800–5600 cal BC). Settled at the intersection of wide alluvial plains, waterlogged meadows and marshes to the east, and forested hills to the west, early farmers at Alsónyék had a wide variety of options for nourishing their livestock. We performed stable isotope ratio analysis of bone collagen (n = 99; δ13C, δ15N) and tooth enamel (nteeth = 28, sequentially sampled for δ13C and δ18O) from wild and domestic animals to locate them in the landscape and investigate herding practices on a seasonal scale. The bone collagen isotope ratios mostly indicate feeding in open environments. However, results from the sequential analysis of cattle and sheep enamel suggest diverse dietary strategies for winters, including consumption of forest resources, consumption of summer hay and grazing in an open environment. Most pigs appear to have had herbivorous diets, but several individuals likely supplemented their diet with animal protein. Stable isotope ratio results from the Lengyel phase at Alsónyék (ca. 4800–4300 cal BC) suggest more access to animal protein for pigs, and feeding in more open areas by wild boar, red deer and cattle compared to the Starčevo phase. This study’s results demonstrate considerable variability in early animal husbandry practices at Alsónyék.

Metformin in the prevention of type 2 diabetes after gestational diabetes in postnatal women (OMAhA): a UK multicentre randomised, placebo-controlled, double-blind feasibility trial with nested qualitative study

Por: Bolou · A. · Drymoussi · Z. · Lanz · D. · Amaefule · C. E. · Gonzalez Carreras · F. J. · Pardo Llorente · M. d. C. · Dodds · J. · Pizzo · E. · Thomas · A. · Heighway · J. · Harden · A. · Sanghi · A. · Hitman · G. · Zamora · J. · Perez · T. · Huda · M. S. B. · Thangaratinam · S.
Objective

To determine the feasibility of a definitive trial of metformin to prevent type 2 diabetes in the postnatal period in women with gestational diabetes.

Design

A multicentre, placebo-controlled, double-blind randomised feasibility trial with qualitative evaluation.

Setting

Three inner-city UK National Health Service hospitals in London.

Participants

Pregnant women with gestational diabetes treated with medication.

Interventions

2 g of metformin (intervention) or placebo (control) from delivery until 1 year postnatally.

Primary outcome measures

Rates of recruitment, randomisation, follow-up, attrition and adherence to the intervention.

Secondary outcome measures

Preliminary estimates of glycaemic effects, qualitative exploration, acceptability of the intervention and costs.

Results

Out of 302 eligible women, 57.9% (175/302) were recruited. We randomised 82.3% (144/175) of those recruited, with 71 women in the metformin group and 73 women in the placebo group. Of the participants remaining in the study and providing any adherence information, 54.1% (59/109) took at least 75% of the target intervention dose; the overall mean adherence was 64% (SD 33.6). Study procedures were found to be acceptable to women and healthcare professionals. An increased perceived risk of developing type 2 diabetes, or a positive experience of taking metformin during pregnancy, encouraged participation and adherence to the intervention. Barriers to adherence included disruption to the medication schedule caused by the washout periods ahead of each study visit or having insufficient daily reminders.

Conclusions

It is feasible to run a full-scale definitive trial on the effectiveness of metformin to prevent type 2 diabetes in women with gestational diabetes, during the early postnatal period. Adherence and engagement with the study could be improved with more regular reminders and potentially the addition of ongoing educational or peer support to reinforce messages around type 2 diabetes prevention.

Trial registration number

ISRCTN20930880.

Scabies outbreak management in refugee/migrant camps in Europe 2014-2017: a retrospective qualitative interview study of healthcare staff experiences and perspectives

Por: Richardson · N. A. · Cassell · J. A. · Head · M. G. · Lanza · S. · Schaefer · C. · Walker · S. L. · Middleton · J.
Objectives

Provide insights into the experiences and perspectives of healthcare staff who treated scabies or managed outbreaks in formal and informal refugee/migrant camps in Europe 2014–2017.

Design

Retrospective qualitative study using semistructured telephone interviews and framework analysis. Recruitment was done primarily through online networks of healthcare staff involved in medical care in refugee/migrant settings.

Setting

Formal and informal refugee/migrant camps in Europe 2014–2017.

Participants

Twelve participants (four doctors, four nurses, three allied health workers, one medical student) who had worked in camps (six in informal camps, nine in formal ones) across 15 locations within seven European countries (Greece, Serbia, Macedonia, Turkey, France, the Netherlands, Belgium).

Results

Participants reported that in camps they had worked, scabies diagnosis was primarily clinical (without dermatoscopy), and treatment and outbreak management varied highly. Seven stated scabicides were provided, while five reported that only symptomatic management was offered. They described camps as difficult places to work, with poor living standards for residents. Key perceived barriers to scabies control were (1) lack of water, sanitation and hygiene, specifically: absent/limited showers (difficult to wash off topical scabicides), and inability to wash clothes and bedding (may have increased transmission/reinfestation); (2) social factors: language, stigma, treatment non-compliance and mobility (interfering with contact tracing and follow-up treatments); (3) healthcare factors: scabicide shortages and diversity, lack of examination privacy and staff inexperience; (4) organisational factors: overcrowding, ineffective interorganisational coordination, and lack of support and maltreatment by state authorities (eg, not providing basic facilities, obstruction of self-care by camp residents and non-governmental organisation (NGO) aid).

Conclusions

We recommend development of accessible scabies guidelines for camps, use of consensus diagnostic criteria and oral ivermectin mass treatments. In addition, as much of the work described was by small, volunteer-staffed NGOs, we in the wider healthcare community should reflect how to better support such initiatives and those they serve.

Eficacia del tratamiento para las personas agitadas en situaciones de emergencia en comparación con los servicios comunitarios: revisión sistemática

Objetivo: Conocer la eficacia del tratamiento de personas con conducta hetero agresiva en los servicios de urgencias en comparación con los servicios de salud comunitarios. Método: Revisión sistemática de estudios en bases de datos: LILACS, Psychinfo, Scopus, Web de Ciencia, PUBMED y literatura gris en Google Scholar y en la lista de referencias. La búsqueda se realizó en junio de 2016. Dos mil ciento sesenta estudios fueron encontrados y seis de estos estudios fueron seleccionados para su análisis después de la aplicación de los criterios de exclusión. Resultados: El acercamiento a individuos con comportamiento agitado, agresivo o violento ocurre con mayor frecuencia en servicios de emergencia general y psiquiátrica con intervención médica. Los medicamentos utilizados para controlar la agitación y la sedación fueron benzodiazepina (midazolam, lorazepam), antihistamínico (prometazina), antipsicóticos típicos (haloperidol y droperidol) y antipsicóticos atípicos (olanzapina, ziprasidona, risperidona y quetiapina). Conclusión: Todos los fármacos evaluados promueven la sedación, pero esta revisión muestra ventajas en el uso de la combinación de haloperidol más prometazina.

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